The stromal-vascular fraction of adipose tissue contributes to major differences between subcutaneous and visceral fat depots

Abstract Introduction Obesity is a potent risk factor for the development of kidney disease (CKD). The localization of adipose tissue and its hormonal activity plays an important role in the formation of the cardiorenal relationship. Purpose of work To assess the relationship between visceral fat stores with hormonal activity of adipose tissue, metabolic parameters and markers of renal dysfunction in patients with borderline arterial hypertension (AH) and obesity. Materials and methods The study included 100 people aged 44.8±6.4 years. Group 1 – patients with borderline hypertension – SBP 134.1±4.7 mm Hg; DBP – 84.3±5.9 mm Hg, BMI 36.1±3.2kg/m2. Group 2 was patients with BMI 35.5±3.9 kg/m2, SBP level 120.6±10.1 mm Hg and DBP 70.1±8.4 mm Hg. Albumin/creatinine ratio urine (ACRU), β2 microglobulin, tumor necrosis factor (TNF), interleukin 6 (IL6), monocytechemoattractant protein (MCP-1) was determined in a single portion of morning urine, the level of leptin, resistin and cystatin C was determined by ELISA. Glomerular filtration rate (GFR) was calculated using the CKD-EPI formula and cystatin C (Hoek's formula). The examination of visceral adipose tissue (VAT) was using an ultrasound method of investigation: the epi- and pericardial fat depots were assessed; VAT 1 – measurement at the level of the navel from the inner surface of the rectus abdominis to the posterior wall of the aorta and L4; VAT 2 – measurement at the level of the navel from the inner surface of the rectus abdominis to L4; the thickness of the posterior perirenal VAT on the right and left and the area of perirenal fat on both sides. Result The amount of fat depots in the groups is shown in Table 1. Indicators of hormonal activity of adipose tissue and renal markers are presented in Table 2. In the group with borderline hypertension the relationship between VAT 1 and 2 with ALT levels (r=0.40) and (r=0.42) was established, AST (r=0.52) and (r=0.47); HDL (r=−0.67) and (r=−0.70), TG (r=0.38) and (r=0, 39), HOMA index (r=0.45) and (r=0.39), MCP-1 (r=0.28) and (r=0.36). Perineal fat depot located to the right and left is correlated with LDL (r=0.40) and (r=0.37), glucose (r=0.49) and (r=0.50), ACRU (r=0.43) and (r=0.57), urinary excretion of cystatin C (r=0.28) and (r=0, 39). The connection with the optimal blood pressure level in control group was established between the perineal adipose tissue on the right and the left with the level of TG (r=0.35) and (r=0.29), GFR according to Hoek (r=0.29) and (r=0, 38), MCP-1 (r=0.36) and (r=0.29). Findings The increase of perinephral adipose tissue in obese patients is associated with an increase in cytokine excretion in the urine, an increase in VAT is accompanied by a deterioration in metabolic parameters. FUNDunding Acknowledgement Type of funding sources: None.

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TWEAK prevents TNF-α-induced insulin resistance through PP2A activation in human adipocytes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00589.2012 ◽

2013 ◽

Vol 305 (1) ◽

pp. E101-E112 ◽

Cited By ~ 18

Author(s):

Ana Vázquez-Carballo ◽

Victòria Ceperuelo-Mallafré ◽

Matilde R. Chacón ◽

Elsa Maymó-Masip ◽

Margarita Lorenzo ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Insulin Signaling ◽

Visceral Fat ◽

Molecular Mechanisms ◽

Physiological Role ◽

Metabolic Effects ◽

Human Adipocytes ◽

Fat Depots ◽

Tnf Α

Visceral fat is strongly associated with insulin resistance. Obesity-associated adipose tissue inflammation and inflammatory cytokine production are considered key mediators of insulin signaling inhibition. TWEAK is a relatively new member of the TNF cytokine superfamily, which can exist as full length membrane-associated (mTWEAK) and soluble (sTWEAK) isoforms. Although TWEAK has been shown to have important functions in chronic inflammatory diseases its physiological role in adipose tissue remains unresolved. In this study, we explore the molecular mechanisms involved in the modulation of TNF-α-induced effects on insulin sensitivity by sTWEAK in a human visceral adipose cell line and also in primary human adipocytes obtained from visceral fat depots. Our data reveal that sTWEAK ameliorates TNF-α-induced insulin resistance on glucose uptake, GLUT4 translocation and insulin signaling without affecting other metabolic effects of TNF-α such as lipolysis or apoptotis. Co-immunoprecipitation experiments in adipose cells revealed that pretreatment with sTWEAK specifically inhibits TRAF2 association with TNFR1, but not with TNFR2, which mediates insulin resistance. However, sTWEAK does not affect other downstream molecules activated by TNF-α, such as TAK1. Rather, sTWEAK abolishes the stimulatory effect of TNF-α on JNK1/2, which is directly involved in the development of insulin resistance. This is associated with an increase in PP2A activity upon sTWEAK treatment. Silencing of the PP2A catalytic subunit gene overcomes the dephosphorylation effect of sTWEAK on JNK1/2, pointing to PP2A as a relevant mediator of sTWEAK-induced JNK inactivation. Overall, our data reveal a protective role of TWEAK in glucose homeostasis and identify PP2A as a new driver in the modulation of TNF-α signaling by sTWEAK.

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Abdominal adipose tissue: Significance and methods of detection

Medicinski pregled ◽

10.2298/mpns0506258s ◽

2005 ◽

Vol 58 (5-6) ◽

pp. 258-264 ◽

Cited By ~ 6

Author(s):

Biljana Srdic ◽

Edita Stokic ◽

Agneza Polzovic ◽

Sinisa Babovic

Keyword(s):

Adipose Tissue ◽

Body Fat ◽

Visceral Fat ◽

Fat Distribution ◽

Body Fat Distribution ◽

Abdominal Adipose Tissue ◽

Fat Depots ◽

Advantages And Disadvantages ◽

Increased Risk ◽

Menopausal Women

Introduction. The presence of excess fat in the abdomen, out of proportion to total body fat, is associated with increased risk for cardiovascular and metabolic diseases and other complications of obesity. Histoanatomical characteristics of the abdominal adipose tissue In regard to subcutaneous fat, accumulation of visceral abdominal adipose tissue is more associated with increased metabolic risk. However, mean have more visceral fat than pre-menopausal women. Compared with pre-menopausal women, postmenopausal women have 49% more intraabdominal fat, regardless of age and total fat mass. Measurement of abdominal fat depots Various anthropometric indicators have been suggested for measuring body fat distribution. All of them have advantages and disadvantages, in relation to their interpretation and use. Many are specified as ratios and are difficult to interpret biologically, whereas a change in body fat distribution may exhibit little or no change in the ratios. Waist circumference and sagittal abdominal diameter are good predictors of visceral fat. But, extreme individual variations in visceral to subcutaneous ratio demonstrate the limitations of external anthropometry. The best methods to estimate the amount of visceral fat are imaging techniques like computed tomography or magnetic resonance, but they are expensive and inconvinient in routine practice. Conclusion. Further investigations should provide a simple and optimal indicator of abdominal obesity which should correlate with the amount of viscelar fat and the risk. .

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Glucocorticoid reamplification within cells intensifies NF-κB and MAPK signaling and reinforces inflammation in activated preadipocytes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00320.2009 ◽

2010 ◽

Vol 298 (5) ◽

pp. E930-E940 ◽

Cited By ~ 33

Author(s):

Takako Ishii-Yonemoto ◽

Hiroaki Masuzaki ◽

Shintaro Yasue ◽

Sadanori Okada ◽

Chisayo Kozuka ◽

...

Keyword(s):

Adipose Tissue ◽

Reductase Activity ◽

Stromal Vascular Fraction ◽

Mapk Signaling ◽

Obese Mice ◽

Monocyte Chemoattractant Protein 1 ◽

Protein Levels ◽

Fat Depots ◽

Tnf Α

Increased expression and activity of the intracellular glucocorticoid-reactivating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) contribute to dysfunction of adipose tissue. Although the pathophysiological role of 11β-HSD1 in mature adipocytes has long been investigated, its potential role in preadipocytes still remains obscure. The present study demonstrates that the expression of 11β-HSD1 in preadipocyte-rich stromal vascular fraction (SVF) cells in fat depots from ob/ob and diet-induced obese mice was markedly elevated compared with lean control. In 3T3-L1 preadipocytes, the level of mRNA and reductase activity of 11β-HSD1 was augmented by TNF-α, IL-1β, and LPS, with a concomitant increase in inducible nitric oxide synthase (iNOS), monocyte chemoattractant protein-1 (MCP-1), or IL-6 secretion. Pharmacological inhibition of 11β-HSD1 and RNA interference against 11β-HSD1 reduced the mRNA and protein levels of iNOS, MCP-1, and IL-6. In contrast, overexpression of 11β-HSD1 further augmented TNF-α-induced iNOS, IL-6, and MCP-1 expression. Moreover, 11β-HSD1 inhibitors attenuated TNF-α-induced phosphorylation of NF-κB p65 and p38-, JNK-, and ERK1/2-MAPK. Collectively, the present study provides novel evidence that inflammatory stimuli-induced 11β-HSD1 in activated preadipocytes intensifies NF-κB and MAPK signaling pathways and results in further induction of proinflammatory molecules. Not limited to 3T3-L1 preadipocytes, we also demonstrated that the notion was reproducible in the primary SVF cells from obese mice. These findings highlight an unexpected, proinflammatory role of reamplified glucocorticoids within preadipocytes in obese adipose tissue.

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ASSOCIATION BETWEEN PERIRENAL ADIPOSE TISSUE AND OTHER VISCERAL FAT DEPOTS IN PATIENTS WITH ABDOMINAL OBESITY

Journal of Hypertension ◽

10.1097/01.hjh.0000748380.22705.a7 ◽

2021 ◽

Vol 39 (Supplement 1) ◽

pp. e335

Author(s):

Natalia Blinova ◽

Marina Azimova ◽

Yulia Zhernakova ◽

Ekaterina Zheleznova ◽

Makka Azimova ◽

...

Keyword(s):

Adipose Tissue ◽

Abdominal Obesity ◽

Visceral Fat ◽

Perirenal Adipose Tissue ◽

Fat Depots

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Interleukins 6 and 15 Levels Are Higher in Subcutaneous Adipose Tissue, but Obesity Is Associated with Their Increased Content in Visceral Fat Depots

International Journal of Molecular Sciences ◽

10.3390/ijms161025817 ◽

2015 ◽

Vol 16 (10) ◽

pp. 25817-25830 ◽

Cited By ~ 22

Author(s):

Marta Jonas ◽

Alina Kurylowicz ◽

Zbigniew Bartoszewicz ◽

Wojciech Lisik ◽

Maurycy Jonas ◽

...

Keyword(s):

Adipose Tissue ◽

Visceral Fat ◽

Subcutaneous Adipose Tissue ◽

Fat Depots ◽

Subcutaneous Adipose

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Large-Scale Analysis of Circulating Amino Acids and Gene Expression in Relation to Abdominal Obesity

10.1101/2020.11.19.388678 ◽

2020 ◽

Author(s):

Maltais-Payette Ina ◽

Vijay Jinchu ◽

Simon Marie-Michelle ◽

Grundberg Elin ◽

Tchernof André

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Abdominal Obesity ◽

Expression Profiles ◽

Stromal Vascular Fraction ◽

Cell Types ◽

Abdominal Fat ◽

Fat Accumulation ◽

Fat Depots ◽

Potential Biomarker

AbstractBackgroundCirculating branched-chain amino acid (BCAA) levels are increased in obesity. One hypothesis explaining this phenomenon is downregulated catabolism in adipose tissue. Glutamate is a byproduct of this pathway and was found to be positively associated with central fat accumulation. We assessed the association between circulating glutamate and abdominal obesity, and how it relates to gene expression pathways in abdominal fat depots and cell types.MethodsWe used logistic regression to assess the odds of presenting abdominal obesity with varying circulating glutamate in 4,665 individuals from the TwinsUK cohort. We also compared glutamate levels in twin pairs discordant for abdominal obesity. We accessed gene expression profiles of adipose tissue and cells across depots derived from independent cohorts for phenotype, differential expression and pathway analysis.ResultsIndividuals in the 5th quintile of circulating glutamate had a 7-fold increase in the risk of presenting abdominal obesity compared to those in the 1st quintile. This risk was greater than that associated with being in the 5th quintile of either BCAAs. Twins with abdominal obesity had significantly higher glutamate levels than their leaner co-twins. Most genes of the BCAA catabolism pathway were more expressed in the stromal vascular fraction (SVF) compared to adipocytes and associated with abdominal obesity in both men and women. Among the top pathways to be upregulated in visceral SVF was the glutamate receptor signaling pathway.ConclusionGlutamate is a potential biomarker of abdominal fat accumulation. Differences in gene expression across adipose tissue depots and cell types reflect this association.

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Adipocyte Fatty Acid-Binding Protein, Cardiovascular Diseases and Mortality

Frontiers in Immunology ◽

10.3389/fimmu.2021.589206 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chi-Ho Lee ◽

David T. W. Lui ◽

Karen S. L. Lam

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Visceral Fat ◽

Fatty Acid Binding Protein ◽

Inflammatory Responses ◽

Binding Protein ◽

Fatty Acid Binding ◽

Fat Depots ◽

Acid Binding Protein

It has been increasingly recognized that inflammation plays an important role in the pathogenesis of cardiovascular disease (CVD). In obesity, adipose tissue inflammation, especially in the visceral fat depots, contributes to systemic inflammation and promotes the development of atherosclerosis. Adipocyte fatty acid-binding protein (AFABP), a lipid chaperone abundantly secreted from the adipocytes and macrophages, is one of the key players mediating this adipose-vascular cross-talk, in part via its interaction with c-Jun NH2-terminal kinase (JNK) and activator protein-1 (AP-1) to form a positive feedback loop, and perpetuate inflammatory responses. In mice, selective JNK inactivation in the adipose tissue significantly reduced the expression of AFABP in their adipose tissue, as well as circulating AFABP levels. Importantly, fat transplant experiments showed that adipose-specific JNK inactivation in the visceral fat was sufficient to protect mice with apoE deficiency from atherosclerosis, with the beneficial effects attenuated by the continuous infusion of recombinant AFABP, supporting the role of AFABP as the link between visceral fat inflammation and atherosclerosis. In humans, raised circulating AFABP levels are associated with incident metabolic syndrome, type 2 diabetes and CVD, as well as non-alcoholic steatohepatitis, diabetic nephropathy and adverse renal outcomes, all being conditions closely related to inflammation and enhanced CV mortality. Collectively, these clinical data have provided support to AFABP as an important adipokine linking obesity, inflammation and CVD. This review will discuss recent findings on the role of AFABP in CVD and mortality, the possible underlying mechanisms, and pharmacological inhibition of AFABP as a potential strategy to combat CVD.

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Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00059.2011 ◽

2011 ◽

Vol 301 (4) ◽

pp. E599-E607 ◽

Cited By ~ 42

Author(s):

Le Zhang ◽

Philip J. Ebenezer ◽

Kalavathi Dasuri ◽

Sun Ok Fernandez-Kim ◽

Joseph Francis ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Adipose Tissue ◽

Visceral Fat ◽

Subcutaneous Fat ◽

Reactive Oxygen ◽

The Body ◽

Oxygen Species ◽

Fat Depots ◽

Tissue Aging

As a part of aging there are known to be numerous alterations which occur in multiple tissues of the body, and the focus of this study was to determine the extent to which oxidative stress and hypoxia occur during adipose tissue aging. In our studies we demonstrate for the first time that aging is associated with both hypoxia (38% reduction in oxygen levels, Po2 21.7 mmHg) and increases reactive oxygen species in visceral fat depots of aging male C57Bl/6 mice. Interestingly, aging visceral fat depots were observed to have significantly less change in the expression of genes involved in redox regulation compared with aging subcutaneous fat tissue. Exposure of 3T3-L1 adipocytes to the levels of hypoxia observed in aging adipose tissue was sufficient to alter multiple aspects of adipose biology inducing increased levels of in insulin-stimulated glucose uptake and decreased lipid content. Taken together, these data demonstrate that hypoxia and increased levels of reactive oxygen species occur in aging adipose tissue, highlighting the potential for these two stressors as potential modulators of adipose dysfunction during aging.

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