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Visceral fat and inflammation markers

Visceral fat and inflammation markers

conceived and designed the study. Viscceral Markers onflammation Delineate Murine Znd and M2 Macrophages. PubMed Electrolyte Replacement Central Google Scholar. Article Understanding BMI Google Pumpkin Seed Tea Benezech C, Luu NT, Walker JA, Kruglov AA, Loo Y, Nakamura K, et al. Fernandez-Real JMGutierrez CRicart WCastineira MJVendrell JRichart C Plasma levels of the soluble fraction of tumor necrosis factor receptors 1 and 2 are independent determinants of plasma cholesterol and LDL-cholesterol concentrations in healthy subjects. D'Agostino, Sr. Visceral fat and inflammation markers

Visceral fat and inflammation markers -

Interestingly, adjusting for SAT index of central SAT or hip circumference index of peripheral SAT did not reduce the importance of VAT for predicting systemic inflammatory markers. Our findings suggest that both BMI and VAT are correlates of systemic inflammation in obese subjects with type 2 diabetes.

Furthermore, VAT provides information additional to BMI for a number of systemic inflammatory markers that are strongly associated with vascular remodeling and coagulation 13 , , , , — An increase in inflammatory markers has been associated with increased risk for metabolic abnormalities and cardiovascular disease 2 , 5 , Expansion of adipose tissue explains these associations, as it promotes a systemic inflammatory response.

Inflammatory molecules such as TNF-α, IL-6, serum amyloid A, and MCP-1 are produced in significant quantity by ATMs and adipocytes 2 , 5 , Both SAT and VAT are known to secrete inflammatory cytokines in vitro and have been implicated in metabolic disorders 7 , — 9.

Subcutaneous abdominal fat is divided into superficial and deep layers by a fascial plane, and recent evidence suggests that there maybe metabolic differences between the two components For example, deep but not superficial subcutaneous abdominal tissue has been associated with peripheral insulin resistance and features of metabolic syndrome We were not able to separate these compartments in the current study.

A recent study from the Framingham cohort has shown that both VAT and SAT are associated with CRP and a number of other inflammatory markers, independent of BMI; however, the associations were stronger for VAT Therefore, while our data affirm the importance of adipose tissue distribution on inflammatory markers in obese subjects even after the onset of diabetes, they also suggest that relationships between specific adipose tissue depots and inflammatory markers may be modified by the onset of diabetes.

Similar to previous studies, we observed sex differences in CRP and fibrinogen levels with higher levels in women We also found a stronger association between CRP and BMI, independent of VAT and SAT, in women. In multivariable fully adjusted models, an increase in VAT was strongly associated with an increase in PAI-1 levels independent of BMI.

A higher PAI-1 plasma level has been linked to a higher risk of coronary heart disease in subjects with type 2 diabetes Both animal and human studies suggest that PAI-1 expression is higher in VAT than SAT 9 , Our data support the strong association between VAT and PAI-1 levels, independent of BMI, in type 2 diabetes.

MCP-1 is a potent chemotactic factor for monocytes 23 and has been associated with cardiovascular disease and diabetes In the Framingham cohort, MCP-1 was more strongly associated with VAT than with SAT Our findings are similar to the Framingham cohort, as we also observed a strong correlation between VAT and MCP-1 that was independent of BMI.

ICAM-1 and VCAM-1 are members of the cellular adhesion molecule family that have been implicated in inflammatory and atherosclerotic processes Elevated levels of both have been reported in obesity In the Framingham cohort, both SAT and VAT were associated with ICAM-1 but neither of these relations persisted after adjustment for BMI In contrast, in our study, VAT was associated with ICAM-1 before and after adjustment for BMI.

In contrast to findings in predominantly nondiabetic populations, we found no independent relationships among BMI, VAT or SAT, and fibrinogen or MMP9 in fully adjusted models 11 , Although prospective studies will be necessary to determine the causal nature of these associations, our results suggest that in obese subjects with type 2 diabetes, both BMI and VAT are important drivers of systemic inflammation.

While BMI is strongly associated with CRP and IL-6 levels, VAT is the primary determinant of ICAM, VCAM, MCP-1, and PAI ICAM and VCAM are found in the vessel wall where their level of expression is related to atherosclerotic plaque remodeling 13 , 17 , MCP-1 and PAI-1 are significant markers of cardiovascular disease risk 14 , — Our findings indicate that adipose tissue distribution remains an important determinant of systemic inflammation in type 2 diabetes.

They underscore the importance of managing excess adiposity, including that in the visceral fat depot, for optimally managing cardiovascular risk in subjects with type 2 diabetes. The costs of publication of this article were defrayed in part by the payment of page charges.

Section solely to indicate this fact. This analysis was supported by National Institutes of Health Grant DK to T. and by an institutional award from the University of Illinois at Chicago. No other potential conflicts of interest relevant to this article were reported.

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User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 32, Issue 5. Previous Article Next Article. RESEARCH DESIGN AND METHODS.

Article Navigation. Cardiovascular and Metabolic Risk February 19 Relation of Abdominal Fat Depots to Systemic Markers of Inflammation in Type 2 Diabetes Susan Sam, MD ; Susan Sam, MD. This Site. Google Scholar. Steven Haffner, MD ; Steven Haffner, MD. Michael H. Davidson, MD ; Michael H.

Davidson, MD. Ralph B. D'Agostino, Sr. Steven Feinstein, MD ; Steven Feinstein, MD. George Kondos, MD ; George Kondos, MD. Alfonso Perez, MD ; Alfonso Perez, MD.

Theodore Mazzone, MD Theodore Mazzone, MD. Corresponding author: Theodore Mazzone, tmazzone uic. Diabetes Care ;32 5 — Article history Received:. Get Permissions. toolbar search Search Dropdown Menu. Bruun JM, Lihn AS, Pedersen SB, Richelsen B: Monocyte chemoattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue AT : implication of macrophages resident in the AT.

Download references. This work was supported by grants from the Kurozumi Medical Foundation, Tanita Healthy Weight Community Trust, The Japan Health Foundation, and Grant-in-Aid for Scientific Research of Japan Society for the Promotion of Science and for Exploratory Research from Ministry of Education, Culture, Sports, Science and Technology, Japan.

The authors gratefully acknowledge Drs. Kazuyuki Yoshizaki and Seiji Takashima who participated in the health examination. Health Care Center, Osaka University, Machikaneyama, Toyonaka, Osaka, , Japan. You can also search for this author in PubMed Google Scholar.

Correspondence to Keiko Yamauchi-Takihara. TM, YS and KYT conceived the study and participated in its design and coordination. MN performed the statistical analysis. MN and KYT drafted the manuscript and interpreted the data. All authors read and approved the final version of the manuscript.

Open Access This article is published under license to BioMed Central Ltd. Reprints and permissions. Nishida, M. et al. Abdominal obesity exhibits distinct effect on inflammatory and anti-inflammatory proteins in apparently healthy Japanese men.

Cardiovasc Diabetol 6 , 27 Download citation. Received : 24 July Accepted : 01 October Published : 01 October Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

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Download ePub. Abstract Background Since visceral fat tissue is known to release various inflammatory and anti-inflammatory cytokines, abdominal obesity may play a key role in the inflammation associated with metabolic syndrome MetS.

Methods Subjects consisted of apparently healthy Japanese men age: 30 to 59 years who underwent health examination in the Osaka University Health Care Center. Conclusion Inflammatory status is not exaggerated by clustering of MetS components in the subjects without abdominal obesity.

Methods Study population A total of apparently healthy Japanese men, 30 to 59 years of age, who underwent health examination in the Osaka University Health Care Center, were evaluated with MetS components. Risk factor assessment Waist circumference at the umbilical level was measured in the late exhalation phase in standing position.

Statistical analysis All values are mean ± SD. Results Profiles of the study subjects are shown in Table 1. Table 1 Characteristics of the study subjects Full size table. Figure 1. Full size image. Table 2 Difference in mean values of risk factors between the subjects with "High" and "Low" inflammatory markers Full size table.

Table 3 Correlation between serum adiponectin and hs-CRP levels in obesity and abdominal obesity groups Full size table. Discussion It is considered that clustering of metabolic abnormalities presents synergistic effects on cardiovascular complications beyond the sum of effects of individual abnormalities [ 19 ].

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Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Subjects and Methods. Journal Article. The Metabolic Syndrome in Obese Postmenopausal Women: Relationship to Body Composition, Visceral Fat, and Inflammation.

Tongjian You , Tongjian You. Tongjian You, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina Oxford Academic. Alice S.

Barbara J. PDF Split View Views. Cite Cite Tongjian You, Alice S. Select Format Select format. ris Mendeley, Papers, Zotero. enw EndNote. bibtex BibTex. txt Medlars, RefWorks Download citation. Permissions Icon Permissions.

Abstract The purpose of this study was to investigate whether aerobic fitness, body composition, body fat distribution, and inflammation are different in obese postmenopausal women with and without the metabolic syndrome MS , and whether the severity of MS is associated with these characteristics.

TABLE 1. Number of MS components in all women. of MS components. Open in new tab. TABLE 2. TABLE 3. Open in new tab Download slide. high density lipoprotein cholesterol;. Google Scholar PubMed.

OpenURL Placeholder Text. Effects of age on body fat distribution and cardiovascular risk factors in women. Effects of the menopause transition on body fatness and body fat distribution. Google Scholar Crossref.

Inflammaion SamSteven HaffnerMichael H. DavidsonRalph B. D'Agostino Understanding BMI, Steven AnndGeorge Kondos Vieceral, Alfonso PerezVisceral fat and inflammation markers Mazzone; Relation of Diabetes management support Fat Depots to Systemic Markers of Inflammation in Type 2 Diabetes. Diabetes Care 1 May ; 32 5 : — Both visceral adipose tissue VAT and subcutaneous adipose tissue SAT have been linked to systemic inflammation in nondiabetic cohorts. We examined the relationships between VAT and SAT and systemic inflammatory markers in a large well-characterized cohort of subjects with type 2 diabetes. Thank you for visiting Electrolyte Replacement. You are using a aft version with limited support for CSS. Electrolyte Replacement obtain the makers experience, we recommend you Dental crowns and bridges Understanding BMI more Understanding BMI to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. In adults, upper body fat partially increases metabolic disease risk through increasing systemic inflammation. Our objective was to determine if this relationship exists in preschool-aged children.

BMC Medicine volume 20Article number: Cite this article. Metrics details. Obesity usually is accompanied by inflammation of fat tissue, with a prominent role of visceral fat. Appetite suppressants for cravings inflammation in obese fat Viscsral is of a lower grade than acute immune Understanding BMI Viscsral clearing the tissue Electrolyte Replacement inflammatjon infectious agent.

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Eventual lipid overload of hypertrophic adipocytes leads to Natural sweeteners for desserts reticulum stress and the secretion of Viscsral variety of signals causing increased sympathetic tone, inflxmmation by adipocytes, adn uptake by macrophages, matrix remodeling, angiogenesis, and immune cell activation.

Wnd signaling of inflamation causes the resident immune system to release increased amounts of pro-inflammatory and mar,ers mediators resulting in enhanced tissue-protective responses. With chronic overnutrition, these inflmamation actions are insufficient, and death of adipocytes as Body composition scanning device as senescence Viceral several tissue cell types is seen.

This structural damage causes the Visferal or release of immunostimulatory Liver detoxification plan components resulting in influx and activation of monocytes and many Vissceral immune cell types, with a contribution inlfammation stromal cells.

Matrix remodeling and angiogenesis is further intensified mwrkers well markerrs possibly detrimental fibrosis. The accumulation of senescent cells also ihflammation be detrimental via eventual inlammation of senescence state from affected to neighboring cells by the marekrs of microRNA-containing vesicles.

Obese visceral fat inflammation can Visceral fat and inflammation markers viewed as an initially protective response in order to cope with excess ambient Quick appetite control and restore Dehydration and caffeine homeostasis but may contribute to tissue damage unflammation a later stage.

Peer Review reports. Fat tissue is Prediabetes treatment Visceral fat and inflammation markers Martial Arts and Self-defense immune cells iinflammation are all other solid tissues of the body, Visceral fat and inflammation markers.

Activation inflammqtion such immune cells usually is accompanied by local or systemic inflammation of varying Viscerla. Mild responses include local insulin Pre-game meal ideas, oxidative stress and altered cell metabolism.

Increase mental agility degrees of inflammation are characterized by Thermogenic supplements for women activation faf infiltration of circulating immune cells which may cause local pain, edema, or fever [ 1 inglammation, 2 inflammatjon.

The present review ibflammation changes in visceral fat tissue in response to chronic overnutrition, the signals and cell types involved in the early stages of tissue inflammation, marmers the progression to full-blown inflammation characterized by tissue damage and infiltration of circulating immune cells.

In visceral fat, members of the innate as Anti-cancer initiatives as adaptive immune system have been identified.

These include Ac and immune system function, dendritic cells, granulocytes, innate lymphoid cells ILCs and natural killer Mxrkers cellsand also T and B cells [ nad ] Fig.

Marker transcriptome analysis of mouse lean inflammatiom adipose inflamjation leukocytes identified 15 distinct Visveral [ 4 ]. In normal aand tissue, these cells mmarkers not only immune guardians against infection inflammatoon also support proper tissue markefs.

Many of these findings originate from studies in experimental models, but where analyzed, inflammatiob physiological functions of immune cells Hydration strategies also been reported in humans [ 5 ].

For instance, macrophages exhibit functional Antioxidant vegetables which inflammafion the Mindful eating practices of dead or apoptotic markkers cells, remodeling the extracellular matrix and fag angiogenesis [ 5 ].

A subtype of macrophages supports the Viscwral of lipid metabolism mwrkers uptake and digestion of lipids inflammmation 67 ]. Furthermore, the secretion of IL appears onflammation be a major Visceeal of promoting thermogenesis in fat cells [ 8 Understanding BMI.

Macrophages contribute to the regulation inflwmmation thermogenesis in response to cold exposure [ 9 ]. There is no homogeneous distribution of macrophage subtypes.

For instance, in human subcutaneous tissue, spatial mapping identified macrophages with a M1-like phenotype associated with niches of adipocyte Pancreatic beta cells cells while Understanding BMI with a non-inflammatory Body cleanse for improved immunity were dispersed throughout Artificial Hormone-Free Dairy fat tissue [ Visceeral ].

Network Viaceral physiological functions of resident immune cells in lean visceral adipose tissue. Belly fat reduction inspiration the Leafy green supplements of metabolic or Viscearl stress resident immune cells interact among themselves and with ffat and stromal cells inflammatio maintain proper tissue inflammaton.

There are no signature cytokines defining the maintenance state of resident immune cells. Cytokines, chemokines, acute phase Visceeal, and other immune mediators vat released in small amounts mostly from resident immune cells but also Visceal mesenchymal stromal cells inflamjation adipocytes.

Several macrophage subtypes promote matrix remodeling and angiogenesis, Visceral fat and inflammation markers dead cell inflammstion lipid aggregates, anx promote adipocyte thermogenesis.

Viisceral also inflxmmation adipocyte thermogenesis and stimulates physiological eosinophil functions. Regulatory T cells promote Protein and hormone regulation repair and interact with macrophages and Mental performance supplements for youth immune cell far to maintain a non-inflammatory state.

Low-level secretion of immune mediators by macrophages, dendritic cells, and other immune cell types such as ILC2s, iNKTs, Th2 cells, γδT cells, B-1b cells, and eosinophils helps to prevent immune cell activation.

For better readability, only a few key intercellular signals are included in the scheme. ATM, adipose tissue macrophage; DC, dendritic cell; IL, interleukin; ILC, innate lymphoid cell; iNKT, innate natural killer T cell; MetEnk, methionine-enkephalin peptides; NK, natural killer cell.

ILC2 cells contribute to the regulation of energy expenditure by promoting the differentiation of beige adipocytes from adipocyte precursors or beiging of white fat cells in visceral tissues via upregulation of uncoupling protein 1 UCP1 by enkephalin peptides [ 1112 ].

ILC2-derived IL helps to prevent pro-inflammatory activation of macrophages, dendritic cells, ILC1, and natural killer cells. By secreting IL-5, ILC2 cells promote anti-inflammatory eosinophil activity. Conventional dendritic cells exhibit a tolerogenic phenotype, characterized by IL production and suppression of Th1-promoting activity by upregulated expression of peroxisome proliferator-activated receptor gamma PPAR-γ [ 13 ].

Regulatory T cells Treg represent the major CD4-positive T cell type, they participate in tissue repair and preserve Glut-4 expression by adipocytes [ 1415 ]. Interestingly, the majority of Tregs appear to be oligoclonal in mice as indicated by distinct T cell receptor repertoires.

There may be MHC II-dependent antigen recognition involved, as suggested by the close association with resident macrophages and dendritic cells [ 16 ].

The primary function of Tregs probably is to keep other immune cell types in a neutral physiological state, i. Resident B-1b lymphocytes secrete natural IgM antibodies and promote adipose physiological functions by suppressing B-2 cells, in mice and humans [ 17 ]. In addition, B-1 cells comprise the major cell type of fat-associated lymphoid clusters which appear to contribute to humoral immune responses to peritoneal antigens [ 18 ].

Lymphoid clusters in mice and humans are also a rich source of Th2-like cytokines released from innate Th2-like lymphoid cells [ 1920 ]. Fat-associated lymphoid clusters such as milky spots on the omentum surface probably serve immune functions of the peritoneal cavity rather than supporting physiological fat tissue functions.

Indeed, the numbers of milky spots increase during peritoneal inflammation in response to local TNFα and innate natural killer T cell activity [ 2021 ]. Studies in mice suggest that sympathetic innervation is promoted by γδT cells by signaling via the IL receptor C to induce TGFß1 production by parenchymal cells [ 22 ].

Further, sympathetic neuron-associated macrophages SAMs regulate neuron growth and modulate adrenergic signaling [ 23 ]. Based mostly on animal studies, the continuous release of anti-inflammatory mediators from macrophages, dendritic cells, Th2-cells, γδT cells, eosinophils, mucosa-associated invariant T cells MAITand invariant natural killer T cells appears to further help maintain metabolic homeostasis [ 14242526272829303132 ] Fig.

The support of tissue functions by resident immune cells involves interactions with non-immune tissue cells including adipocytes, endothelial cells, neurons, fibroblasts, and other mesenchymal stromal cells [ 33334 ]. In the absence of immunologic stimuli, immune mediator secretion from resident immune cells and other fat tissue cells is low.

The local immune milieu is well buffered, i. Further, pro-inflammatory TNFα and ILA induce counterregulatory IL for the stimulation of anti-inflammatory Tregs and ILC2s [ 153536 ].

Taken together, in lean visceral adipose tissue, there is a physiological network of adipocytes, stromal cells, and immune cells. The resident immune system is not dormant but supports overall tissue functions. Cytokines, chemokines, acute phase proteins, and other immune mediators are released in small amounts mostly from resident immune cells but also from mesenchymal stromal cells and adipocytes [ 3738 ].

The primary cause of progression from lean to obese visceral fat tissue is excess calorie intake, including digestible carbohydrates.

Human metabolic control usually is geared in such a way that a calorie surplus is not disposed of by generating additional thermal energy but is stored to a large degree as triglycerides in adipocytes.

Excess calorie consumption causes an increase of circulating insulin levels after and between meals. Being an anabolic hormone, insulin suppresses lipolysis and promotes fat storage in adipocytes already at concentrations that are in the high normal range or which are slightly elevated.

Pharmacological or experimental lowering of insulin levels indeed ameliorates obesity which indicates that the support of lipogenesis by insulin is obesogenic reviewed by [ 39 ].

These regulatory effects of insulin do not apply for all adipocytes. In subcutaneous tissue about half of mature adipocytes are insulin responsive, the two other subtypes exhibit little or no increased transcriptional activity when exposed to hyperinsulinemia [ 10 ].

Anabolic activity of visceral fat tissue in response to overnutrition involves adipocyte enlargement and hyperplasia to accommodate for increased requirements of energy storage, i. Lipogenesis leads to enlargement of mature adipocytes because of more fat stored in one large lipid droplet organelle.

There is also differentiation and growth of preadipocytes, but in visceral fat hyperplasia contributes less to the increase of fat mass than adipocyte hypertrophy [ 41 ].

The formation of new fat-laden adipocytes from precursor cells appears to begin when enlarged mature adipocytes reach a critical cell size and release mediators stimulating preadipocyte growth and differentiation [ 4243 ].

Fat cell hyperplasia thus is a second pathway of coping with excess circulating nutrients Fig. Response of visceral fat tissue to excess calories by adipocyte hypertrophy and hyperplasia. In response to high levels of circulating glucose, triglycerides, and the anabolic hormone insulin mature adipocytes take up increased amounts of nutrients and store excess energy as triglycerides in one large lipid droplet organelle.

The cell size may increase 10—fold in diameter. Enlarged adipocytes secrete factors favoring angiogenesis and remodeling of the extracellular matrix and release of growth factors which is essential for mesenchymal stem cells, adipocyte progenitors, and preadipocytes to differentiate into lipid-storing mature adipocytes.

In parallel, macrophages are stimulated to support angiogenesis and matrix remodeling. ATM, adipocyte tissue macrophages; TGs, triglycerides; Glc, glucose; ECM, extracellular matrix; Pro-inflamm.

Studies in mice indicate that a major obstacle to fat tissue expansion in response to high-fat diet feeding is the collagen network of the extracellular matrix.

A major source of collagen is perivascular cells in response to signaling via the platelet-derived growth factor 1α [ 44 ]. Most relevant for limiting fat tissue expansion is the extracellular matrix of niches rich in adipocyte precursors.

Interestingly, these niches harbor potentially pro-inflammatory macrophages [ 10 ] and induction of acute local inflammation, for instance by injection of low-dose lipopolysaccharide enhances fibrolysis and remodeling of the extracellular matrix, and promotes angiogenesis to allow for efficient adipocyte hyperplasia.

Enlarged adipocytes initiate fat tissue remodeling by secreting angiogenic factors such as such as fibroblast growth factor-2, vascular endothelial growth factor, human growth factor, and other mediators such as extracellular matrix proteases Fig. Efficient remodeling requires activation of pro-inflammatory macrophages by hypertrophic adipocytes which appears to be a physiological response needed for fat tissue growth because downregulation of pro-inflammatory reactivity prevents proper adipocyte hyperplasia [ 414546 ].

Thus, at least initially, inflammation in adipose tissue is a physiological adaptive response which improves fat tissue plasticity and consequently preserves metabolic control and insulin sensitivity [ 47 ].

A similar important role of inflammatory reactions, such as activation of the NLRP3 inflammasome, has been reported to drive postburn white adipose tissue remodeling [ 48 ]. Storage of energy in form of triglycerides also occurs in other fat tissues of the body, notably subcutaneous fat.

The adipogenic activity and the ability to mobilize preadipocytes in response to overeating have been reported to be delayed in subcutaneous fat and therefore may be insufficient to lower the metabolic stress of visceral fat tissue during excess calorie intake [ 43 ].

However, this is different in persons with true metabolic healthy obesity, i. In these persons, the growth of visceral fat and adipocyte enlargement is only moderate, and excess nutrients are primarily handled by enlargement and hyperplasia of adipocytes in subcutaneous fat tissue, primarily in the superficial layer [ 43505152 ].

In sum, the primary fat tissue response to excess calorie intake includes enlargement of adipocytes, differentiation of new mature cells from pre-adipocytes or stem cells, all supported by remodeling of the extracellular matrix, and of angiogenesis for appropriate blood supply.

Growth of visceral fat tissue is not possible without appropriate remodeling of the vasculature and the extracellular matrix surrounding preadipocytes and small adipocytes. Enlarged adipocytes initiate these changes by secreting factors promoting angiogenesis and matrix remodeling.

These adaptive responses are characteristic of metabolically healthy obesity. A recent overview of inflammatory responses to non-infectious stimuli in various tissues of the body has concluded that there appear to be three types of perturbation causing an inflammatory response which, at least initially, are considered protective [ 2 ] The suggested hierarchy of perturbations is loss of regulation, loss of function and loss of structure.

This concept is applied here to obese fat tissue, and the current section considers loss of regulation.

: Visceral fat and inflammation markers

Obese visceral fat tissue inflammation: from protective to detrimental? | BMC Medicine | Full Text Article CAS Google Magkers Foley KP, Chen Y, Football player nutrition NG, Heal Understanding BMI, Kwok K, Viscetal AK, et al. Xu X, Grijalva A, Skowronski A, van EM SMJ, Ferrante Electrolyte Replacement Jr. The inflammatiion mediator of Understanding BMI in visceral fat released by adipocytes in obesity is fibronectin type III domain-containing protein 4 FNDC4 which probably targets the receptor GRP In obesity, adipocytes are enlarged, and their secretory properties are altered [ 11 ]. Relation of Abdominal Fat Depots to Systemic Markers of Inflammation in Type 2 Diabetes Susan Sam, MD ; Susan Sam, MD. Kintscher U, Hartge M, Hess K, Foryst-Ludwig A, Clemenz M, Wabitsch M, et al.
Obese visceral fat tissue inflammation: from protective to detrimental? Email alerts Article activity alert. With the exception of SAT, relations of VAT, BMI, and WC to hs-CRP appeared to be stronger in women than in men. Leitzmann; Relations of Visceral and Abdominal Subcutaneous Adipose Tissue, Body Mass Index, and Waist Circumference to Serum Concentrations of Parameters of Chronic Inflammation. Article CAS Google Scholar Marques BG, Hausman DB, Martin RJ. Article Google Scholar Vieira, V. Article CAS Google Scholar Guzman-Ruiz R, Tercero-Alcazar C, Lopez-Alcala J, Sanchez-Ceinos J, Malagon MM, Gordon A. There is secretion of IFNα from plasmacytoid dendritic cells [ 58 ].
Regional adiposity and markers of inflammation in pre-school age children | Scientific Reports Intriguingly, the brown adipose tissue marker UCP1 was modestly higher in old mice, while remained unchanged by the intervention. Although antigens presented have not been identified, it is remarkable that mice with genetic depletion of MHC II in adipocytes gain weight as control mice but do not develop adipose tissue inflammation and insulin resistance [ 71 ]. The increased local release of noradrenaline also promotes lipolysis. To our knowledge, this is a unique study, given the paucity of prospective studies across the menopausal transition. The possible reason for the nonsignificant results may be due to the relatively small sample size in the study. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Horm Metab Res 35 : —
Background

In parallel, macrophages are stimulated to support angiogenesis and matrix remodeling. ATM, adipocyte tissue macrophages; TGs, triglycerides; Glc, glucose; ECM, extracellular matrix; Pro-inflamm. Studies in mice indicate that a major obstacle to fat tissue expansion in response to high-fat diet feeding is the collagen network of the extracellular matrix.

A major source of collagen is perivascular cells in response to signaling via the platelet-derived growth factor 1α [ 44 ]. Most relevant for limiting fat tissue expansion is the extracellular matrix of niches rich in adipocyte precursors.

Interestingly, these niches harbor potentially pro-inflammatory macrophages [ 10 ] and induction of acute local inflammation, for instance by injection of low-dose lipopolysaccharide enhances fibrolysis and remodeling of the extracellular matrix, and promotes angiogenesis to allow for efficient adipocyte hyperplasia.

Enlarged adipocytes initiate fat tissue remodeling by secreting angiogenic factors such as such as fibroblast growth factor-2, vascular endothelial growth factor, human growth factor, and other mediators such as extracellular matrix proteases Fig.

Efficient remodeling requires activation of pro-inflammatory macrophages by hypertrophic adipocytes which appears to be a physiological response needed for fat tissue growth because downregulation of pro-inflammatory reactivity prevents proper adipocyte hyperplasia [ 41 , 45 , 46 ].

Thus, at least initially, inflammation in adipose tissue is a physiological adaptive response which improves fat tissue plasticity and consequently preserves metabolic control and insulin sensitivity [ 47 ]. A similar important role of inflammatory reactions, such as activation of the NLRP3 inflammasome, has been reported to drive postburn white adipose tissue remodeling [ 48 ].

Storage of energy in form of triglycerides also occurs in other fat tissues of the body, notably subcutaneous fat. The adipogenic activity and the ability to mobilize preadipocytes in response to overeating have been reported to be delayed in subcutaneous fat and therefore may be insufficient to lower the metabolic stress of visceral fat tissue during excess calorie intake [ 43 ].

However, this is different in persons with true metabolic healthy obesity, i. In these persons, the growth of visceral fat and adipocyte enlargement is only moderate, and excess nutrients are primarily handled by enlargement and hyperplasia of adipocytes in subcutaneous fat tissue, primarily in the superficial layer [ 43 , 50 , 51 , 52 ].

In sum, the primary fat tissue response to excess calorie intake includes enlargement of adipocytes, differentiation of new mature cells from pre-adipocytes or stem cells, all supported by remodeling of the extracellular matrix, and of angiogenesis for appropriate blood supply. Growth of visceral fat tissue is not possible without appropriate remodeling of the vasculature and the extracellular matrix surrounding preadipocytes and small adipocytes.

Enlarged adipocytes initiate these changes by secreting factors promoting angiogenesis and matrix remodeling. These adaptive responses are characteristic of metabolically healthy obesity.

A recent overview of inflammatory responses to non-infectious stimuli in various tissues of the body has concluded that there appear to be three types of perturbation causing an inflammatory response which, at least initially, are considered protective [ 2 ] The suggested hierarchy of perturbations is loss of regulation, loss of function and loss of structure.

This concept is applied here to obese fat tissue, and the current section considers loss of regulation. In those visceral adipose regions where the adaptive response to excess energy influx has reached a limit, metabolic homeostasis is lost, and activation of resident immune cells occurs.

In detail, strongly enlarged adipocytes fail to maintain metabolic homeostasis of lipid storage versus lipolysis because the lipid overload leads to endoplasmic reticulum stress, increased expression of the inflammation regulator NF-kB and the production of inflammation-inducing signals such as IL-6 [ 40 , 53 ].

The secretion of pro-inflammatory mediators in response to loss of metabolic homeostasis has been termed metaflammation [ 54 ]. Enlarged adipocytes exhibit additional responses to caloric stress. For instance, adipocytes respond to high ambient nutrient concentrations with the release of leptin and other hormones which target the brain to limit food intake and increase the sympathetic tone.

Adrenaline and noradrenaline are released from nerve endings in adipose tissue and activate lipolysis by signaling via ß-adrenergic receptors of adipocytes. Sympathetic neuron-associated macrophages may function as rate-limiters by degrading noradrenaline via monoamine oxidase A [ 23 ].

The locally increased concentration of non-esterified fatty acids is expected to activate pro-inflammatory macrophage functions. This may involve co-secretion of adipocyte fatty acid binding protein FABP4 , induction of FABP4 in macrophages, and signaling via toll-like receptors TLR4 and TLR2.

Free fatty acids do not directly bind to TLR4, but lipid metabolism within macrophages is affected by the influx of free fatty acids which has pro-inflammatory consequences if there is simultaneous activation of TLR4.

The latter may result from increased levels of lipopolysaccharide released from gut microbiota in the context of gut leakiness during an obesogenic diet [ 55 , 56 , 57 , 58 , 59 , 60 ]. Further, recent studies suggest a role of adenine nucleotide translocase 2 in mediating free fatty acid-induced mitochondrial dysfunction, increased oxygen radical production and NF-kB activation in fat tissue macrophages [ 61 ].

The secretion of leptin by enlarged adipocytes not only limits food intake and promotes lipolysis in visceral fat but also engages leptin receptors present on most immune cells.

Another pathway of promoting local inflammation in response to adipocyte enlargement is activated by rapid fat tissue growth in the presence of insufficient angiogenesis which lowers capillary density and increases diffusion distance for oxygen eventually resulting in a hypoxic environment of enlarged adipocytes.

Adipose is among the most vascularized tissues with each adipocyte surrounded by capillaries [ 63 ]. Lowering ambient oxygen concentration in adipocyte culture caused a switch from oxidative phosphorylation to anaerobic glycolysis and changed the expression of more than genes [ 64 ].

One major mediator of this response is hypoxia-inducible factor 1α [ 55 ]. Pro-inflammatory mediators secreted by mature adipocytes during hypoxia include chemokines and cytokines such as PAI-1, CCL5, and IL-6 as well as micro RNAs [ 65 , 66 , 67 , 68 ] Fig.

A subset of macrophages is closely associated with the vasculature and characterized by the expression of lymphatic vessel endothelial hyaluronan receptor 1. These macrophages support angiogenesis by producing tissue remodeling growth factors and metalloproteinases [ 21 , 69 ].

Hypoxia does not homogeneously affect visceral fat tissue but is a regional phenomenon as concluded from immunohistochemical staining for hypoxia-inducible factor 1α. The colocalization of enhanced numbers of macrophages and T cells supports the pro-inflammatory property of hypoxia [ 70 ].

Local inflammation in response to disturbed adipocyte metabolic homeostasis. When enhanced lipid storage via adipocyte enlargement and differentiation of progenitor cells fails to maintain metabolic homeostasis, local inflammatory changes occur in order to dispose of excess lipid and regain metabolic control.

For one, lipid-laden adipocytes experience endoplasmic reticulum stress and increased expression of NFkB leading to the release of pro-inflammatory mediators such as IL Additional pro-inflammatory signals are delivered by the release of free fatty acids, leptin, lipopolysaccharides, and other products of an unbalanced microbiota in the context of a leaky gut.

Activated resident immune cells release amounts of pro-inflammatory mediators sufficient to promote lipolysis and suppress lipid storage in part via induction of insulin resistance. In addition, there is an uptake of lipids by macrophages and storage in small lipid droplets.

Leptin interacts with receptors in the brain to limit food intake and increase the sympathetic tone. The increased local release of noradrenaline also promotes lipolysis.

Another pro-inflammatory condition results from hypoxia due to local enlargement of adipocytes. The concomitant release of enzymes and factors promoting tissue remodeling and angiogenesis may be considered a healing response.

Enlarged adipocytes overexpress MHC class II antigens and appear to present antigens to CD4-positive T cells. Another pathway of limiting energy storage is the induction of adipocyte beiging by transdifferentiation or growth from progenitors and the disposal of excess energy by thermogenesis.

A third pathway of pro-inflammatory activation of resident immune cells is suggested by the finding that hypertrophic adipocytes overexpress major histocompatibility antigens class II MHCII and produce costimulatory molecules for effective antigen presentation to CD4 positive T cells.

Although antigens presented have not been identified, it is remarkable that mice with genetic depletion of MHC II in adipocytes gain weight as control mice but do not develop adipose tissue inflammation and insulin resistance [ 71 ].

An additional pathway of lowering the metabolic stress in obese visceral fat tissue is the transdifferentiation of white adipocytes to beige adipocytes and the formation of new beige adipocytes from precursor cells Fig. Beige adipocytes contain several smaller lipid droplet organelles and more mitochondria than hypertrophic adipocytes for burning free fatty acids to generate heat.

Secretion of IL from macrophages promotes thermogenesis in fat cells [ 8 ], as does the release of enkephalin peptides from ILC2 cells [ 11 , 12 ]. The major mediator of beiging in visceral fat released by adipocytes in obesity is fibronectin type III domain-containing protein 4 FNDC4 which probably targets the receptor GRP There is a positive association between the expression of FNDC4 and obesity-associated inflammation [ 72 ].

In line with a role in regaining normal tissue homeostasis, FNDC4 exhibits anti-inflammatory properties in macrophages [ 73 ]. Taken together, loss of metabolic homeostasis in fat tissue is sufficient to initiate a local pro-inflammatory response.

Secretion of pro-inflammatory mediators from macrophages and other immune cells substantially exceeds the release from adipocytes [ 38 ]. This may be viewed as an attempt to restore proper energy balance [ 74 ]. The locally enhanced concentrations of mediators like TNFα, IL-1, and IL-6 act back on adipocytes and suppress further lipid storage by inhibiting lipoprotein lipase, needed for lipid uptake, and by promoting lipolysis and fatty acid release via several pathways.

These include the local induction of insulin resistance in insulin-sensitive adipocytes resulting from engaging TNFα or other pro-inflammatory mediators including microRNAs and subsequent impairment of insulin signaling for lipolysis inhibition [ 26 , 75 ].

Further support comes from increased activation of extracellular signal-regulated kinase ERK stimulating beta3 adrenergic receptor-mediated lipolysis via protein kinase A [ 76 ]. Inflammatory stress induces kinase activity of inositol-requiring protein 1 IRE-1 , a component of the endoplasmic reticulum stress response, which is also followed by enhanced lipolysis [ 77 ].

In addition, there is upregulation of lysosomal biogenesis, increased uptake and turnover of lipids, and increased formation of lipid droplets in macrophages, all of which can be considered an attempt to lower the lipid load of adipocytes [ 78 ].

The interaction between the various cell types in adipose tissue can also be described as crosstalk since there is signaling between cells in both directions. Crosstalk not only involves the secretion of soluble mediators but also of particulate structures such as extracellular vesicles or mitochondria [ 79 , 80 ].

The scenario described relates to observations in animal models. In humans, the direct demonstration an early phase of inflammatory reactions induced by metabolically stressed enlarged adipocytes during overnutrition would require repeated biopsies of visceral fat tissue, but the mechanisms detailed above also apply to human cells.

In mice, high-fat diet feeding studies observed an early period of 4—8 weeks with adipocyte enlargement, limited local immune activation, vasculogenesis, matrix remodeling, and clearance of a low number of dead adipocytes by local macrophages [ 81 ].

A general characteristic of tissue damage is the loss of structural integrity, i. Many of these molecules are immunostimulatory damage-associated molecular patterns DAMPs , they include stress proteins, high mobility group box 1 protein HMGB1 , DNA, some lipids, and mitochondrial structures, among many others.

DAMP receptors also called pattern recognition receptors are present on innate immune cells and in part also on adaptive immune cells and non-immune cells such as epithelial cells, endothelial cells, or fibroblasts.

DAMP receptors include toll-like receptors, C-type lectin receptors, cytoplasmic NLR receptors, and several DNA sensors. Signaling via these receptors leads to the production of pro-inflammatory cytokines and other mediators [ 82 , 83 ].

Dead adipocytes accumulate in obese visceral tissue and attract resident macrophages giving the image of crown-like structures resulting in phagocytic activity and proliferation. Apoptotic adipocytes express surface proteins favoring phagocytosis by M2-type macrophages [ 84 ].

Treg cells also associate with crown-like structures and probably support non-inflammatory macrophage functions [ 14 ]. However, probably because of the size difference of macrophages and hypertrophic dying adipocytes, there is also lysosomal exocytosis, and the released DAMPs stimulate pro-inflammatory immune activities which are more M1- than M2-like [ 85 ].

Immune activation by DAMPs appears to exceed pro-inflammatory signaling caused by metabolically stressed adipocytes because there is an influx of monocytes and other immune cells which outnumber resident immunocytes [ 55 , 84 ].

In mouse fat tissue, induction of inflammasome and caspase-1 activity for the release of IL-1 and IL is required for the recruitment of circulating immune cells and their pro-inflammatory activation [ 86 ]. Secretion of macrophage chemotactic protein 1 MCP-1 also contributes to monocyte attraction [ 87 , 88 ].

These cells exhibit impaired cell functions and an irreversible proliferative arrest in association with the secretion of a variety of pro-inflammatory cytokines, chemokines, proteases, and vesicles containing microRNAs, DNA, lipids, and protein.

Peptides secreted in the context of the senescence-associated secretory phenotype SASP not only stimulate adipocytes and activate resident immune cells but also help recruit circulating immune cells to fat tissue followed by their activation [ 58 , 89 , 90 , 91 ].

Structural damage also ensues if physiological remodeling of the extracellular matrix of obese visceral fat tissue is insufficient to adapt to tissue growth and enhanced angiogenesis. Collagen accumulates around adipocytes and in fiber bundles leading to decreased tissue plasticity.

This leads to an adipocyte-mediated release of endotrophin, a cleavage product of collagen VI, which enhances local inflammatory responses [ 92 , 93 , 94 ]. The findings described above suggest that the recruitment of immune cells and their accumulation occurs in response to structural damage of visceral fat tissue Fig.

The dominant immune cells in the infiltrate are monocytes developing into tissue macrophages. Concomitantly, there is an influx of other immune cell types, including T and B cells, ILC1s, ILC3s, NK cells, mast cells, and neutrophils [ 25 , 30 , 94 , 95 , 96 , 97 , 98 , 99 ].

Since the fat tissue is not homogeneous with regard to vascularization, hypoxia, and adipocyte death, there is regional diversity of the inflammatory state. Severe visceral fat tissue inflammation in response to structural disruption. Excessive enlargement of adipocytes in response to chronic overnutrition eventually causes structural damage with dying adipocytes and cell senescence as hallmarks.

The phagocytotic capacity of macrophages is overwhelmed and released DAMPS strongly activate resident immune and endothelial cells resulting in the attraction of virtually all types of immune cells.

Their pro-inflammatory activation also stimulates anti-inflammatory activities. Another structural change is the accumulation of senescent cells, mostly macrophages, pre-adipocytes, mature adipocytes, and endothelial cells. Senescent cells secrete pro-inflammatory mediators and enhance the accumulation of immune cells from circulation.

DAMPs and free fatty acids do not exhibit the same strong immunostimulatory activity as seen for bacterial or viral components. In inflamed obese visceral tissue infiltrated by immune cells, there is an overall dominance of pro-inflammatory activity.

This situation is best researched for macrophages, which remain the prominent immune cell type in inflamed obese visceral tissue with structural damage, largely due to the recruitment of monocytes from circulation. Most infiltrated macrophages are polarized towards a pro-inflammatory phenotype which only partially resembles classic M1-like activity characterized by the secretion of IL-1ß, IL, TNFα, chemokines, and proteases [ ].

As discussed above, pro-inflammatory cytokines such as TNFα elicit the production of anti-inflammatory cytokines such as IL or of prostaglandin E2. There is regional diversity between macrophages within and outside crown-like structures, and in other human obese visceral adipose tissue [ 85 ].

For instance, macrophages with adipogenic and angiogenic gene expression patterns are distributed more evenly in the visceral fat tissue while lipid-laden pro-inflammatory macrophages are associated with dead adipocytes [ 85 ].

Obesity induced by long-term feeding of a high-fat diet in mice also changes the major phenotype of dendritic cells in visceral fat towards a pro-inflammatory profile.

There is secretion of IFNα from plasmacytoid dendritic cells [ 58 ]. In parallel, the number of regulatory T cells, supporting the maintenance function of immune cells, is decreasing.

The loss of Treg lymphocytes from obese visceral tissue appears to be a direct consequence of IFNα action [ 58 ]. The lower number of regulatory T cells may be the major reason accounting for a pro-inflammatory shift in several other immunocytes.

Early changes include an influx of pro-inflammatory T cells and of B lymphocytes. In high-fat diet-induced obesity of mice both cell types appear to precede peak macrophage infiltration [ , ]. IFN γ secretion by CD4- and CD8-positive T lymphocytes as well as of NK cells and ILC1s probably is a strong activator of pro-inflammatory macrophage activity.

Stimulation of T-cells for IFN γ production probably is supported by the pro-inflammatory B2 subset of B lymphocytes while the percentage of anti-inflammatory B1 cells is decreased [ 55 , 97 , , , , , , ]. There is also activation of MAIT cells which promotes macrophage activation by secretion of TNFα and IL [ ].

In the context of visceral obese fat tissue inflammation, there is also an increase of activated neutrophils. These cells release extracellular traps which interact with other immune cells to promote pro-inflammatory responses and possibly contribute to remodeling of the matrix because of the protease content of traps, in addition to promoting insulin resistance [ , ].

Obese visceral fat tissue also harbors increased numbers of mast cells [ ] but it is not clear whether these cells promote or dampen inflammation [ ]. The immune cell influx in response to structural damage of fat tissue appears to exhibit tissue-protective and also detrimental properties.

Fat tissue repair such as elimination of dying adipocytes, enhanced lipolysis, tissue remodeling, and angiogenesis represent beneficial functions of infiltrated and resident immune cells.

However, animal studies indicate that matrix remodeling during chronic inflammation eventually may lead to fibrosis, i. An alternative view suggests that a rigid extracellular membrane prevents excessive enlargement of adipocytes and supports metabolic homeostasis [ ]. Senescent cells in inflamed tissue probably also have beneficial and as well as detrimental effects.

In animal models, beneficial effects include the orchestration of tissue remodeling through the secretion of pro-inflammatory factors. Senescent cells positively impact health span, liver, and vascular tissue fibrosis, and wound healing [ , ].

However, if senescent cells are not cleared within days or weeks by innate immune cells, they accumulate and spread senescence to neighboring and distant cells, mostly via secretion of microRNA-containing vesicles with the consequence of a pro-fibrotic state and deficient tissue function in hypertrophic obesity mice [ 46 , , , ].

Obesity and hyperinsulinemia also drive the senescence of adipocytes or visceral fat macrophages in humans [ 91 , ]. In obese mice, genetic or pharmacological elimination of senescent cells promoted adipogenesis and decreased the influx of monocytes into abdominal fat [ 89 , ].

When human obese visceral tissue containing senescent cells was transplanted into immunodeficient mice, lower glucose tolerance and increased insulin resistance were observed. These detrimental effects were suppressed by clearing the human fat tissue from senescent cells by treatment with a selenolytic cocktail prior to transplantation [ 90 ].

Severe visceral obesity often is accompanied by systemic low-grade inflammation, insulin resistance, glucose intolerance, and other measures of metabolic disturbances. This does not simply appear to be a spill-over effect because there seem to be contributions of other organs such as the liver, the hypothalamus, and the gut microbiota [ , , ].

Overnutrition and excess systemic nutrients cause changes in the liver related to those described for visceral fat. There is enhanced lipid uptake by several cell types followed by disturbed metabolic homeostasis as evident from endoplasmic reticulum stress in hepatocytes.

Eventually, this leads to structural tissue damage such as death of hepatocytes and fibrosis. Loss of metabolic homeostasis and tissue damage is accompanied by activation of the resident immune system.

Pro-inflammatory responses are carried by Kupffer cells, stellate cells, many infiltrated immune cell types, other stromal cell types, and also by hepatocytes [ , , , , , , , ]. In animal models, immune intervention trials often have led to improved metabolic control with or without decreased adiposity indicating a pathogenic role of inflammatory immune reactivity [ , , ].

However, most studies do not allow to distinguish between effects mediated at the level of the liver, pancreas, vasculature, gut, brain, or adipose tissue. A detailed discussion of diet-induced inflammatory changes outside the visceral fat tissue and of immune intervention studies is outside the scope of this paper.

Inflammation of tissues in the absence of infectious, toxic or allergenic agents in general is caused by the local expression of immunostimulatory molecules in the context of metabolic or physical tissue damage.

The activation of resident immune cells as well as the influx of immune cells from circulation into stressed tissue can be interpreted as an attempt to regain the previous physiological balance [ 2 , 74 ]. Loss of structure tissue damage elicits a more intense form of inflammation with influx of circulating immune cells, again primarily supporting tissue functions [ 2 ].

In obese visceral fat tissue, adaptive or repair functions of macrophages and other activated immune cells include support of matrix remodeling and angiogenesis by secretion of proteases and growth factors to accommodate for adipocyte enlargement and hyperplasia, lipid uptake and catabolism to lower lipid load, stimulation of thermogenesis for lipid burning, promotion of lipolysis and local insulin resistance to reduce lipid storage, and clearance from dead adipocytes and senescent cells.

Concomitant fibrosis may be regarded as protective or detrimental, and a low density of senescent cells may favor matrix remodeling. The increase of crown-like structures and the accumulation of senescent cells suggest that repair functions become overwhelmed.

Whether pro-inflammatory activities carried by the immune cell infiltrate from circulation eventually contribute to tissue damage remains to be analyzed. Finally, subtypes of visceral obesity remain to be defined, and not all of them may be represented by animal models. Subtypes may differ with respect to metabolic characteristics, age, sex or genetic background.

The protective versus detrimental functions of inflammation may differ between subtypes. Only articles published in English were selected.

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And he says by contributing to inflammation, visceral fat cells in the abdomen may be doing even more than that. There also is evidence that inflammation plays a role in cancer, and there is even evidence that it plays a role in aging. Someday we may learn that visceral fat is involved in those things, too.

Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S. Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes , published online Feb. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.

Through its affiliations with Barnes-Jewish and St. CSD research informs Senate proposal. Expanded child tax credit would ultimately save money, reduce poverty. Replacing Chevron would have far-reaching implications. The importance of higher purpose, culture in banking.

Brumation and torpor: How animals survive cold snaps by playing dead-ish. Proteins may predict who will get dementia 10 years later, study finds. NEWS ROOM. Sections Find an Expert Media Resources Newsroom Stories Perspectives WashU Experts WashU in the News.

In this abdominal MRI scan, it is possible to see subcutaneous fat around the abdomen, surrounding abdominal muscles. Visceral fat is deeper inside the abdomen, surrounding internal organs.

It is the visceral fat that secretes IL-6, strongly suggesting a mechanistic link to systemic inflammation. Samuel Klein. Luigi Fontana.

Belly fat may drive inflammatory processes associated with disease You Might Inflammatipn Like. Fat Improve executive functions Visceral fat and inflammation markers or foe? Our study parallels the lack of Visceral fat and inflammation markers between MCP-1 fatt Electrolyte Replacement found in other studies 26 In animal models, immune intervention trials often have led to improved metabolic control with or without decreased adiposity indicating a pathogenic role of inflammatory immune reactivity [, ]. Search ADS.

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Visceral Fat Drives Up Inflammation and What You Can Do About It

Visceral fat and inflammation markers -

In obesity, adipocytes are enlarged, and their secretory properties are altered [ 11 ]. Specifically serum levels of tumor necrosis factor alpha TNF-α , interleukin-6 IL-6 , and high-sensitive C-reactive protein hs-CRP are increased, while adiponectin is decreased [ 12 ].

Whether obesity is related to resistin is unclear [ 13,14,15,16,17 ]. Systemic inflammation plays a major role in all stages of atherosclerosis, from initiation over progression to rupture of atherosclerotic plaques [ 18 ].

Moreover, increased circulating levels of hs-CRP, IL-6, and TNF-α are associated with worse cardiovascular outcomes [ 19,20 ]. Previous studies examining the associations between obesity and inflammatory cytokines used BMI, waist circumference WC or waist-to-hip ratio WHR as underlying measure of adiposity [ 16,17,21,22,23,24,25,26,27,28,29,30,31 ].

Because those measures do not differentiate between VAT and SAT, they were unable to fully characterize body fat distribution patterns. Of the studies that did consider body fat distribution, most focused on VAT [ 24,26,32,33,34,35,36,37,38 ], but less is known about the associations between SAT and parameters of systemic chronic inflammation.

Specifically the relation between SAT and hs-CRP has been studied to some extent [ 24,32,33,34,35,37,38,39 ], whereas the associations between SAT and IL-6, TNF-α [ 33,34,37,38,40 ], resistin [ 41,42 ], or adiponectin [ 35,40,43,44 ] have not been targeted sufficiently. In addition, results are inconsistent, and only few studies that examined the relation between VAT or SAT and inflammatory parameters [ 33,38,43 ] reported results from multivariate analyses.

Moreover, no study has compared different measures of obesity with regard to their relations to parameters of chronic inflammation. Thus, we sought to examine the relations of VAT, SAT, BMI, and WC to selected parameters of systemic chronic inflammation in healthy adults.

A cross-sectional study was conducted in Germany between June and August A total of 97 participants 55 women, 42 men aged years were randomly selected through the local population registry. The study was conducted according to the Declaration of Helsinki guidelines and approved by the local ethics committee.

Written informed consent was obtained from all participants. VAT and SAT were quantified using a B-mode ultrasound machine Mindray DP; Mindray Medical Germany GmbH, Darmstadt, Germany and a 3. Measurements were performed according to a strict protocol, details of which are described elsewhere [ 45 ].

Briefly, the method involved multiple image planes that provided information on adipose tissue thickness. The SAT measurement involved one individual image plane at the median line extending from the skin to the linea alba.

VAT was measured using a second image plane reaching from the linea alba to the lumbar vertebra corpus at the median line. All measurements were performed manually by the same examiner at the end of normal expiration applying minimal pressure without displacement of the intra-abdominal contents as verified by the ultrasound image.

The parameters from the images were manually extracted using the electronic onboard caliper and were stored directly in a database. Height and weight were measured with participants wearing underwear without shoes. BMI was calculated by dividing body weight kg by height in meters squared m².

Waist circumference was measured at the mid-point between the lower rib and the iliac crest. Measurements were taken with the participant standing in an upright position. Non-fasting venous blood was drawn by qualified medical staff. Blood was immediately fractionated into serum, plasma, buffy coat, and erythrocytes and aliquoted into straws of 0.

During blood withdrawal and processing, time and room temperature were steadily documented. The straws were stored in conventional tubes at °C.

Serum concentrations of TNF-α, IL-6, resistin, and adiponectin were measured using an enzyme-linked immunosorbent assay Immundiagnostik, Bensheim, Germany , and hs-CRP was determined by immunonephelometry Behring Nephelometer II, Dade Behring, Marburg, Germany.

Potential confounding variables including age, sex, current smoking status, physical activity, use of aspirin or non-steroidal anti-inflammatory drugs NSAIDs , and menopausal status in women were assessed by standardized computer-assisted personal interviews specifically developed for the study.

Smoking status was categorized as currently smoking or non-smoking. Physical activity levels were calculated from metabolic equivalents of task METs by a hour physical activity recall. Drug use during the previous 7 days was documented by pharmaceutical control numbers using codes of the anatomical therapeutic chemical classification system.

Descriptive statistics were calculated using direct standardization according to the age distribution of the study population and stratified by VAT and SAT tertiles. The data regarding hs-CRP, TNF-α, IL-6, resistin, and adiponectin were not distributed normally and were therefore log transformed for further analyses.

We calculated Pearson correlations between measures of obesity and between selected parameters of systemic chronic inflammation. In addition, we calculated partial correlation coefficients between inflammatory parameters adjusted for age, sex, current smoking status, physical activity, menopausal status, and use of aspirin or NSAIDs.

Multivariate linear regression analysis was performed to estimate relations of VAT, SAT, BMI, and WC to hs-CRP, IL-6, TNF-α, resistin, and adiponectin, adjusted for age continuous , sex men; women , smoking status currently smoking; non-smoking , physical activity continuous , menopausal status pre-, peri-, or postmenopausal , and aspirin or NSAID use drug use during the past 7 days: yes; no.

In a second model, all parameters of chronic inflammation were mutually adjusted in addition to the adjustments described in the first model.

In a third model, VAT and SAT were mutually adjusted, and BMI and WC were mutually adjusted. We also ran exploratory analyses stratified by sex, BMI, smoking status, and aspirin or NSAID use. Before fitting the linear regression models, all variables independent and dependent were standardized by subtracting the mean and dividing by the standard deviation to make relations comparable.

IBM SPSS statistics 22 Chicago, IL, USA was used for all analyses. Characteristics of the study population are presented in table 1. The mean age of study participants was In contrast, study subjects with high VAT were less likely to currently smoke than those with low VAT.

There were no appreciable differences in physical activity levels according to VAT. There were no appreciable differences in physical activity levels according to SAT.

The mean concentrations of selected parameters of chronic inflammation were generally higher in men compared to women, with the exception of adiponectin, which was higher in women than in men table 2.

Age-standardized characteristics of participants according to tertiles of VAT and SAT a. No relations of VAT to TNF-α or resistin were found.

No relations of BMI were found to TNF-α or resistin. After mutual adjustment of parameters of systemic chronic inflammation, VAT remained significantly associated with hs-CRP but not with IL-6 or adiponectin table 4.

SAT remained significantly associated with hs-CRP, and BMI remained significantly associated with hs-CRP and adiponectin. WC remained significantly associated with hs-CRP. When VAT and SAT were simultaneously included in the model, only SAT remained significantly associated with hs-CRP.

After mutual adjustment of BMI and WC, BMI remained significantly inversely related to adiponectin. We next conducted an analysis stratified by gender table 5. No statistically significant relations were found between VAT, SAT, BMI, or WC and other inflammatory parameters in men or women, although we noted gender differences for all inflammatory parameters.

With the exception of SAT, relations of VAT, BMI, and WC to hs-CRP appeared to be stronger in women than in men. Inverse relations of VAT, SAT, BMI and WC to TNF-α and to IL-6 were found in women, whereas in men only SAT was inversely related to TNF-α. Relations of VAT, SAT, BMI and WC to IL-6 were stronger in men than in women.

Relations of VAT, SAT, BMI, and WC to selected parameters of systemic chronic inflammation in subgroups defined by sex, BMI, smoking status, and use of aspirin or NSAIDsa. In non-obese participants, no statistically significant relations were found of VAT, SAT, BMI, or WC to any of the inflammatory parameters table 5.

Associations between VAT and inflammatory markers were stronger in current smokers than in non-smokers. In general, VAT, SAT, BMI, and WC were inversely related to TNF-α and IL-6 in users of aspirin or NSAIDs, whereas VAT, BMI, and WC were positively related to these parameters in non-users of aspirin and NSAIDs.

In this population-based study of healthy adults, VAT, SAT, BMI, and WC showed distinct associations with selected parameters of chronic inflammation. Specifically VAT, SAT, BMI, and WC demonstrated a positive relation to hs-CRP. However, the strongest relation was found between SAT and hs-CRP.

Compared to the other anthropometric variables, BMI showed a stronger inverse association with adiponectin. Albeit not significant, VAT was the strongest indicator for increased levels of IL-6 and TNF-α. WC was only weakly related to inflammatory parameters.

These findings were fairly consistent throughout subgroups defined by gender, BMI, current smoking, and use of aspirin and NSAIDs. Similar to our results, previous studies among healthy adults reported that VAT, SAT, BMI, or WC were positively associated with CRP [ 24,32,33,34,38,46 ].

Several investigations reported comparable relations of VAT and SAT to CRP [ 33,38 ] or a stronger association with VAT [ 32,34,37 ], whereas other studies found a stronger relation to SAT [ 35,38,46 ].

However, none of the aforementioned studies mutually adjusted their analyses for inflammatory parameters or for VAT and SAT [ 32,33,34,35,37,38,46 ]. When VAT and SAT were mutually adjusted, we found that only SAT remained significantly associated with hs-CRP, indicating that abdominal SAT may have a pathogenic function, as additionally evidenced by endocrine and inflammatory responses [ 5,10,12,47 ].

That relations of VAT, BMI, and WC to hs-CRP were stronger in women than in men agrees with previous studies [ 21,22,33,38 ] and may be due to enhanced estrogen production in the adipose tissue with upregulation of pro-inflammatory gene expression in women [ 48,49 ].

Our findings in women of similar relations of VAT, SAT, BMI, and WC to hs-CRP suggest that in women associations with CRP are more strongly determined by overall fat mass than by fat distribution.

In contrast, in men we noted that SAT, but not VAT, BMI, or WC, was most strongly associated with CRP, which is consistent with previous studies [ 35,38,46 ] and indicates that adiposity relations with CRP in men may be less strongly influenced by overall fat mass.

Only one previous study stratified the examination by BMI and found no significant association between SAT and CRP in obese subjects [ 37 ]. In contrast to that study, we considered potential confounding variables in multivariate analyses.

In obese individuals, the limited ability of abdominal SAT to store excess energy may cause an increase in free fatty acids FFA flux to the portal vein and the systemic circulation [ 9 ]. Elevated FFA levels are related to increased CRP [ 50 ].

All anthropometric variables showed stronger associations with hs-CRP in current smokers than in non-smokers. Cigarette smoking is associated with increased CRP levels [ 51 ], which may partly reflect the mechanisms believed to underlie the adverse effects of smoking on cardiovascular disease and several types of cancer [ 52 ].

None of the previous studies that examined the relation between adiposity and CRP reported results stratified by smoking status [ 24,32,33,34,38,46 ]. Also, previous studies examining the relations of obesity to CRP and other inflammatory parameters did not report findings stratified by aspirin or NSAIDs use [ 24,32,33,34,38,46 ].

We found that associations of anthropometric factors to hs-CRP were more pronounced among users of aspirin or NSAIDs. Because NSAIDs down-regulate inflammatory cytokine production including CRP [ 53,54 ], we would have expected to observe less pronounced associations with inflammatory parameters among users than among non-users of aspirin or NSAIDs.

Our findings from multivariate analyses without mutual adjustments for inflammatory parameters or for VAT and SAT are consistent with those from previous studies reporting a positive association between VAT and IL-6 [ 33,34,37,38,40 ] and no relation between SAT and IL-6 [ 37,38,40 ].

However, the positive relation of VAT to IL-6 was rendered non-significant after mutual adjustment for other parameters of systemic chronic inflammation and when SAT was included in the model.

In these analyses, we additionally found that associations between VAT and IL-6 were stronger than those between BMI and IL-6, indicating that collecting data on VAT may represent metabolic information captured by IL-6 that is not accounted for by BMI.

Only one previous study stratified its population by gender and reported a stronger relation between VAT and IL-6 in women than in men [ 38 ]. However, that study was limited to elderly individuals, which may explain the difference from our finding.

Men have larger visceral fat depots than women [ 55,56 ,] and IL-6 is predominantly expressed and secreted by VAT [ 57 ]. We found no overall relations of VAT, SAT, BMI, or WC to TNF-α, which is similar to other studies that addressed these associations [ 33,34,37 ].

Albeit not significant, we found a stronger relation of VAT to TNF-α compared to the relations of other obesity measures to TNF-α. In further exploratory analyses, we noted significantly positive relations of VAT to TNF-α and IL-6 among non-users of aspirin or NSAIDs, which may be due to NSAID-mediated down-regulation of inflammatory cytokine production [ 53,54 ].

The available literature includes one study that reported a positive relation between VAT and TNF-α in adults aged 70 to 79 years, but no association between SAT and TNF-α [ 38 ], and another study that found positive relations of both VAT and SAT to TNF-α among obese adolescents [ 40 ].

However, none of these studies mutually adjusted their analyses for inflammatory parameters or for VAT and SAT. We were unable to detect any associations between adiposity measures and resistin levels. This is consistent with most previous studies that found no correlations between markers of adiposity and resistin [ 16,17,29,58,59,60,61,62,63 ], whereas other studies reported a positive relation of obesity to resistin levels [ 15,41,42,64,65,66 ].

Only one population-based study that examined the relation of VAT and SAT to resistin reported results from multivariate analyses and found similar relations of VAT and SAT to resistin in women and no association between VAT and resistin in men [ 42 ].

We found that the relation between SAT and resistin was stronger than the relation of other measures of obesity to resistin.

However, resistin is not expressed by adipocytes but is secreted by macrophages located within adipose tissue depots [ 67 ]. Hence, circulating resistin is not directly related to adiposity levels but to the degree of inflammation within the adipose tissue depots [ 9 ].

Mediators Inflamm. Abbasi, A. Exhaustive exercise modifies different gene expression profiles and pathways in LPS-stimulated and un-stimulated whole blood cultures. Kawanishi, N. Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high-fat-diet-induced obese mice.

PubMed Google Scholar. Oliveira, A. Acute exercise induces a phenotypic switch in adipose tissue macrophage polarization in diet-induced obese rats.

Obesity 21 , — Petrovic, N. Chronic peroxisome proliferator-activated receptor gamma PPARgamma activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes.

Lee, Y. Adipogenic role of alternatively activated macrophages in β-adrenergic remodeling of white adipose tissue. Fischer, K. Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis.

Ruschke, K. Gene expression of PPAR and PGC-1 in human omental and subcutaneous adipose tissues is related to insulin resistance markers and mediates beneficial effects of physical training. Exercise effects on white adipose tissue: Beiging and metabolic adaptations.

Diabetes 64 , — Download references. The authors thank Camilla Sørensen and Anja Jokipii for excellent technical assistance with preparation of the adipose tissue. Also, our deepest gratitude to professor Steen Seier Poulsen, who were instrumental in the immunhistochemical staining, and Ricardo Soares for helping out with the mRNA analysis.

The study was funded by the Nordea Foundation, The Novo Nordisk Foundation, Lundbeck Foundation, and Danish Council for Independent Research Health and Disease.

The Center for Physical Activity Research CFAS , Rigshospitalet, is supported by a grant from TrygFonden. Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Ziegler, A. Damgaard, A. Mackey, P. Schjerling, P. Magnusson, A. Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Healthy and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Department of Physical Therapy, Musculoskeletal Rehabilitation Research Unit, Bispebjerg Hospital, Copenhagen, Denmark.

The Centre of Inflammation and Metabolism and Centre for Physical Activity Research Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

You can also search for this author in PubMed Google Scholar. Ziegler A. planned the experiments. Olesen A. designed the resistance adjusted running wheels.

Damgaard A. and Ziegler A. obtained visceral fat tissue from the mice. L conducted anthropometric, immunohistochemically and immunofluorescence analysis.

Scheele C. established and analyzed mRNA expression in visceral adipose tissue. and Schjerling P. did all the statistical analysis. All authors edited the manuscript, but Ziegler A.

and Kjær M. Correspondence to A. Open Access This article is licensed under a Creative Commons Attribution 4. Reprints and permissions. An anti-inflammatory phenotype in visceral adipose tissue of old lean mice, augmented by exercise.

Sci Rep 9 , Download citation. Received : 04 September Accepted : 07 August Published : 19 August Anyone you share the following link with will be able to read this content:.

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nature scientific reports articles article. Download PDF. Subjects Ageing Chronic inflammation Fat metabolism. Abstract Visceral adipose tissue is an immunogenic tissue, which turns detrimental during obesity by activation of proinflammatory macrophages.

Introduction Adipose tissue is host to various immune cells and it is well established that during obesity, the amount of inflammatory macrophages increase in adipose tissue 1 , 2. Methods Exercise protocol Experiments were conducted in accordance with Danish guidelines Amendment of November 23, as approved by the Danish Animal Inspectorate, Ministry of Justice permit Table 1 Mice randomization and characteristics.

Full size table. Table 2 Training intervention. Figure 1. Full size image. Figure 2. Figure 3. Figure 4. Data Availability All data are freely available upon request. References Xu, H. Article CAS Google Scholar Weisberg, S.

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Author information Author notes A. Ziegler and A. You can also search for this author in PubMed Google Scholar. Correspondence to Keiko Yamauchi-Takihara. TM, YS and KYT conceived the study and participated in its design and coordination. MN performed the statistical analysis.

MN and KYT drafted the manuscript and interpreted the data. All authors read and approved the final version of the manuscript.

Open Access This article is published under license to BioMed Central Ltd. Reprints and permissions. Nishida, M. et al. Abdominal obesity exhibits distinct effect on inflammatory and anti-inflammatory proteins in apparently healthy Japanese men.

Cardiovasc Diabetol 6 , 27 Download citation. Received : 24 July Accepted : 01 October Published : 01 October Anyone you share the following link with will be able to read this content:.

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Abstract Background Since visceral fat tissue is known to release various inflammatory and anti-inflammatory cytokines, abdominal obesity may play a key role in the inflammation associated with metabolic syndrome MetS. Methods Subjects consisted of apparently healthy Japanese men age: 30 to 59 years who underwent health examination in the Osaka University Health Care Center.

Conclusion Inflammatory status is not exaggerated by clustering of MetS components in the subjects without abdominal obesity. Methods Study population A total of apparently healthy Japanese men, 30 to 59 years of age, who underwent health examination in the Osaka University Health Care Center, were evaluated with MetS components.

Risk factor assessment Waist circumference at the umbilical level was measured in the late exhalation phase in standing position. Statistical analysis All values are mean ± SD. Results Profiles of the study subjects are shown in Table 1. Table 1 Characteristics of the study subjects Full size table.

Figure 1. Full size image. Table 2 Difference in mean values of risk factors between the subjects with "High" and "Low" inflammatory markers Full size table. Table 3 Correlation between serum adiponectin and hs-CRP levels in obesity and abdominal obesity groups Full size table.

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Acknowledgements This work was supported by grants from the Kurozumi Medical Foundation, Tanita Healthy Weight Community Trust, The Japan Health Foundation, and Grant-in-Aid for Scientific Research of Japan Society for the Promotion of Science and for Exploratory Research from Ministry of Education, Culture, Sports, Science and Technology, Japan.

View author publications. Additional information Competing interests The author s declare that they have no competing interests. Authors' contributions TM, YS and KYT conceived the study and participated in its design and coordination.

Rights and permissions Open Access This article is published under license to BioMed Central Ltd.

BMC Medicine volume 20Article number: Visceral fat and inflammation markers this article. Inflammatioon details. Imflammation usually Ginseng for memory accompanied markrrs inflammation of fat tissue, Electrolyte Replacement a prominent role marlers visceral fat. Chronic inflammation in obese fat tissue is of a lower grade than acute immune activation for clearing the tissue from an infectious agent. It is the loss of adipocyte metabolic homeostasis that causes activation of resident immune cells for supporting tissue functions and regaining homeostasis. Initially, the excess influx of lipids and glucose in the context of overnutrition is met by adipocyte growth and proliferation.

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