Fatty acid binding protein expression in different adipose tissue depots from lean and obese individuals

Aims/hypothesis: This study investigated the expression of adipose tissue fatty acid binding proteins (FABPs) in subcutaneous and visceral human adipose tissue depots from lean and obese individuals. Methods: Adipocyte lipid binding protein (ALBP) and keratinocyte lipid binding protein (KLBP) expression was quantified by western blot in subcutaneous and omental adipose tissue from 20 obese and 9 lean individuals. RNA expression was quantified by Northern blot in the obese subjects. Results: In the obese subjects, ALBP protein and RNA expression was higher in subcutaneous compared with omental adipose tissue (increases of 31 ± 14 % and 40 ± 13 % respectively, both p < 0.05), whereas in the lean group, KLBP protein levels were 32 ± 9 % lower in subcutaneous fat (p < 0.03). However, the ALBP/KLBP ratio was greater in subcutaneous compared to omental adipose tissue from both lean and obese subjects: increases of 187 ± 71 % (p = 0.01) and 52 ± 23 % (p = 0.17) respectively for the protein ratio, and 21 ± 6 % for RNA (p = 0.01, obese individuals). In lean subjects, insulin concentrations correlated positively with the ALBP/KLBP protein ratio in both depots (both p≤ 0.03). Conclusion/interpretation: There are regional differences in adipose tissue FABP expression, which could be influenced by obesity. However, the ALBP/KLBP ratio is greater in subcutaneous than visceral adipose tissue in lean as well as in obese subjects. Investigation of adipose tissue FABPs could further our understanding of the role of fatty acids in the insulin resistance syndrome. [Diabetologia (2001) 44: 1268–1273] Received: 1 February 2001 and in revised form: 25 June 2001     

Expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tissue in correlation with adipocyte cell volume,serum TNF-alpha,soluble serum TNF-receptor-2 concentrations and C-peptide level

OBJECTIVE: The aim of the study was to evaluate the expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tIssue in correlation with adipocyte cell Volume, serum TNF-alpha, soluble TNF-receptor-2 (sTNFR-2) and indirect parameters of insulin resistance in overweight/obese and lean healthy persons. DESIGN: A cross-sectional case-control study was used. PATIENTS: Twenty-eight overweight/obese probands with normal glucose tolerance (BMI>27 kg/m(2)) and 15 lean people (BMI<25 kg/m(2)), all of them undergoing planned surgical operation, participated in the study. METHODS: Two to four grams of subcutaneous and visceral adipose tIssue were removed and studied using semi-quantitative immunohistochemical staining of the TNF-alpha protein. Serum TNF-alpha, sTNFR-2 (ELISA) and fasting C-peptide (RIA) were measured. RESULTS: TNF-alpha protein was expressed in adipocytes of both depots. The expression was evaluated visually and found to be greater in the obese patients. Significantly higher serum TNF-alpha (5.58+/-0.87 pg/ml vs 4.21+/-0.55, mean+/-s.d., P<0.01, Mann-Whitney) and sTNFR-2 levels (7.84+/-3.56 ng/ml vs 4.59+/-1.35, P=0.005) were found in the obese subgroup in correlation with the fasting C-peptide level (r=0.49, P=0.003; and r=0.74, P=0.001) and the C-peptide/ blood glucose ratio (r=0.47, Spearman, P=0.005; and r=0.70, P=0.001). The cell Volume of both adipocyte depots was found to have a significant positive correlation with serum TNF-alpha and sTNFR-2 levels in the total group of patients (subcutaneous: r=0.52, P=0.0003; r=0.69, P<0.0001; visceral: r=0.65, P<0.0001; r=0.63, P<0.0001) and in both subgroups. CONCLUSIONS: Adipocyte cell Volume of both the subcutaneous and visceral fat depots may be determinants of TNF-alpha, sTNFR-2 production and obesity-linked insulin resistance.     

Glucose uptake and insulin action in human adipose tissue--influence of BMI, anatomical depot and body fat distribution.

OBJECTIVE: To examine and compare in vitro basal and insulin-stimulated glucose uptake in human omental and subcutaneous adipose tissue derived from lean, overweight or obese individuals, and in those with central or peripheral obesity. DESIGN: In vitro study of basal and insulin-stimulated 2-deoxyglucose uptake in human omental and subcutaneous adipose tissue explants derived from patients undergoing elective abdominal surgery. SUBJECTS: Fourteen lean (average age 47 y, average body mass index (BMI) 22 kg/m(2)), 12 overweight (average age 51 y, average BMI 27 kg/m(2)), and 15 obese subjects (average age 45 y, average BMI 39 kg/m(2)). Ten peripherally obese (average age 43 y, average WHR 0.76) and 17 centrally obese (average age 50 y, average waist-to-hip ratio (WHR) 0.92). MEASUREMENTS: Fatness and fat distribution parameters (by anthropometry), basal and insulin stimulated [(3)H]-2-deoxyglucose uptake in omental and subcutaneous adipose tissue explants. RESULTS: In adipose tissue from lean subjects transport of 2-deoxyglucose over basal was stimulated approximately two-fold by insulin. In contrast, 2-deoxyglucose transport in adipose tissue of obese or overweight subjects was not responsive to insulin. Following incubation with 100-nM insulin for 35 min, insulin-stimulated 2-deoxyglucose transport was significantly lower in both omental and subcutaneous adipose tissue of obese and overweight compared to lean subjects. Basal 2-deoxyglucose uptake was also significantly reduced in omental and subcutaneous tissue in obese compared to lean subjects. Depot-specific differences in 2-deoxyglucose uptake were also seen. Overall 2-deoxyglucose uptake was greater in omental than subcutaneous adipose tissue but this was due to increased basal levels rather than increased insulin action. The reduction in insulin-stimulated 2-deoxyglucose uptake seen in overweight and obese subjects was relatively similar in both depots. However, insulin responsive 2-deoxyglucose transport was significantly lower in the omental adipose tissue of subjects with central obesity, as compared to that of subjects with peripheral obesity. No difference in insulin induced 2-deoxyglucose transport was observed in the subcutaneous adipose tissue explants of subjects with either central or peripheral obesity. CONCLUSION: In lean individuals insulin responsiveness of omental and subcutaneous adipose tissue was similar, but basal glucose uptake was significantly higher in omental adipose tissue. Adipose tissue obtained from overweight as well as obese individuals is insulin resistant. This insulin resistance occurs at a lower BMI than previously expected and is not adipose-depot specific. However, in obese subjects with a central distribution of adiposity insulin resistance occurs at the site of omental adipose tissue, in contrast to those with peripheral obesity.     

局部体脂及内分泌脂肪调节激素对瘦素水平的影响

目的　研究中国人非超重、超重及肥胖者瘦素水平与局部体脂、内分泌脂肪调节激素之间的关系。方法　用核磁共振 (MRI)测量 15 0例正常糖耐量的非超重、超重及肥胖者的局部体脂。同时测定瘦素、空腹胰岛素、皮质醇、生长激素、总睾酮、游离睾酮、硫酸去氢表雄酮等内分泌脂肪调节激素。结果　 (1)超重或肥胖者瘦素水平升高 ,女性瘦素水平显著高于男性 ;(2 )体脂对瘦素的影响有性别差异 ,在男性 ,瘦素与腹部皮下脂肪显著相关 (r =0 .75 ,P <0 .0 0 1) ;在女性 ,瘦素与体重指数相关 (r =0 .6 5 ,P <0 .0 0 1) ;(3)胰岛素是独立于体脂之外的调节瘦素的因素 ;(4 )游离睾酮参与瘦素的调节 ,但对瘦素的影响因性别而不同。结论　皮下脂肪是影响瘦素的局部体脂因素 ,胰岛素及雄性激素参与瘦素水平的调节     

Effects of obesity and weight loss on the expression of proteins involved in fatty acid metabolism in human adipose tissue

OBJECTIVE: Disturbances in adipocyte lipolysis in obesity may contribute to elevated circulating non-esterified fatty acid (NEFA) concentrations and insulin resistance. In experimental models, NEFA metabolism is influenced by adipocyte proteins such as adipocyte and keratinocyte lipid binding proteins (aP2/ALBP and mal1/KLBP) and fatty acid translocase (CD36). We investigated the effect of obesity and weight loss on the expression of these proteins in human subcutaneous adipose tissue. STUDY DESIGN AND SUBJECTS: Subcutaneous adipose tissue was obtained from 12 obese (body mass index (BMI) 42.4+/-1.6 kg/m(2)) and 12 lean (23.4+/-0.6 kg/m(2)) subjects. The obese subjects underwent gastric banding and biopsies were taken again after 2 y following a significant weight reduction (BMI 32.8+/-1.4 kg/m(2)). Adipose tissue proteins were quantified by Western blotting. RESULTS: Differential expression of ALBP, KLBP and CD36 was observed in lean and weight-reduced subjects compared with obese individuals. This resulted in a significantly lower ALBP/KLBP ratio in lean and weight-reduced individuals compared to obese subjects. Furthermore there was a significant influence of gender on this ratio. Moreover, the commonly used internal standard protein actin was expressed significantly higher in lean compared to obese individuals. CONCLUSION: The relative content of ALBP and KLBP in human adipose tissue changes with obesity, weight loss and gender indicating differential regulation. Differing responses in the expression patterns of adipose tissue proteins capable of binding NEFAs in response to weight changes suggest a potential importance in the development of obesity-associated complications.     

CC chemokine and CC chemokine receptor profiles in visceral and subcutaneous adipose tissue are altered in human obesity

BACKGROUND/AIMS: Obesity is associated with a low-grade inflammation, insulin resistance, and macrophage infiltration of adipose tissue. The role of CC chemokines and their respective receptors in human adipose tissue inflammation remains to be determined. METHODS: sc and visceral adipose tissue of obese patients (body mass index 53.1 +/- 11.3 kg/m(2)) compared with lean controls (body mass index 25.9 +/- 3.8 kg/m(2)) was analyzed for alterations in inflammatory gene expression. RESULTS: Macrophage infiltration was increased in sc and visceral adipose tissue of obese patients as determined by increased mRNA expression of a macrophage-specific marker (CD68) and by elevated macrophage infiltration. Gene expression of CC chemokines involved in monocyte chemotaxis (CCL2, CCL3, CCL5, CCL7, CCL8, and CCL11) and their receptors (CCR1, CCR2, CCR3, and CCR5) was higher in sc and visceral adipose tissue of obese patients. Serum concentrations of the inflammatory marker IL-6 and C-reactive protein were elevated in obese patients compared with lean controls. Obese patients revealed increased insulin resistance as assessed by the homeostasis model assessment of insulin resistance index and reduced plasma adiponectin concentrations. Adipose tissue expression of many CC chemokines and their receptors in the obese group positively correlated with CD68 expression. CONCLUSION: Up-regulation of the CC chemokines and their respective receptors in adipose tissue occurs in human obesity and is associated with increased systemic inflammation.     

Increased expression of the macrophage markers and of 11beta-HSD-1 in subcutaneous adipose tissue, but not in cultured monocyte-derived macrophages, is associated with liver fat in human obesity

OBJECTIVE: To determine whether increased expression of macrophage markers and of inflammatory markers in subcutaneous adipose tissue is associated with liver fat in human obesity. We also determined whether expression of TNF (gene encoding TNF-alpha), HSD11B1 (gene encoding 11beta-HSD-1) and RETN (gene encoding resistin) in cultured monocyte-derived macrophages differs between obese/overweight and non-obese subjects. DESIGN: Cross-sectional comparison of obese/overweight and non-obese subjects with respect to adipose tissue gene expression, gene expression in monocyte-derived macrophages, liver fat content and in vivo insulin sensitivity. SUBJECTS: Adipose tissue gene expression, gene expression in monocyte-derived macrophages, liver fat content and in vivo insulin sensitivity: 10 healthy non-obese (24.2+/-1.0 kg/m(2)) and 10 healthy obese/overweight (33.1+/-1.7 kg/m(2)) women. Gene expression in monocyte-derived macrophages: seven healthy non-obese (22.1+/-0.7 kg/m(2)) and seven healthy obese/overweight (36.9+/-2.2 kg/m(2)) women. MEASUREMENTS: Adipose tissue biopsies and blood samples for isolation of peripheral mononuclear cells were taken after an overnight fast. Liver fat content was measured using magnetic resonance proton spectroscopy. Whole body insulin sensitivity was measured using the hyperinsulinemic euglycemic clamp technique. Expression levels of TNF, HSD11B1, RETN and the macrophage markers CD68 and ITGAM were determined by real-time PCR. RESULTS: In adipose tissue, expression of HSD11B1, ITGAM and CD68 was significantly increased in the obese/overweight as compared to the non-obese group. Expression of all these genes was closely positively correlated with liver fat content and inversely correlated with whole body insulin sensitivity. The associations between expression of CD68, ITGAM and HSD11B1 and liver fat were independent of obesity. There were no differences in TNF, HSD11B1, RETN or CD68 gene expression basally or after stimulation with lipopolysaccharide in monocyte-derived macrophages between obese/overweight and non-obese subjects. CONCLUSION: Accumulation of fat in the liver is associated with increased adipose tissue inflammation independent of obesity.     

Adipose triglyceride lipase gene expression in human visceral obesity.

In comparison to subcutaneous (SC) fat, visceral adipose tissue is more sensitive to catecholamine-induced lipolysis and less sensitive to the antilipolytic effects of insulin. Variation in the expression of lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) have been reported. We therefore hypothesized that expression of adipose triglyceride lipase (ATGL) is different in visceral and SC depot and investigated whether ATGL mRNA expression is related to obesity, fat distribution and insulin sensitivity. ATGL, LPL, and HSL mRNA expression was measured in 85 paired samples of omental and subcutaneous adipose tissue in normal glucose tolerant lean and obese individuals. In addition, we included a subgroup of obese (BMI >30 kg/m2) individuals with either impaired or preserved insulin sensitivity determined by euglycemic-hyperinsulinemic clamps. ATGL mRNA levels are significantly decreased in insulin resistant obese subjects. Independently of body fat mass, omental ATGL mRNA correlates with fasting insulin concentration, glucose uptake during the steady state of the clamp and HSL mRNA expression. In obese, but not in lean subjects, LPL and HSL mRNA expression was significantly higher in omental compared to SC fat. In both depots, HSL mRNA was significantly lower in obese individuals. Visceral HSL mRNA expression is closely related to adipocyte size and fasting plasma insulin concentrations, whereas visceral fat area significantly predicts visceral LPL mRNA expression. ATGL mRNA expression is not significantly different between omental and SC fat. HSL, but not ATGL mRNA expression is closely related to individual and regional differences in adipocyte size. Impaired insulin sensitivity was associated with decreased ATGL and HSL mRNA expression, independently of body fat mass and fat distribution.     

In humans the adiponectin receptor R2 is expressed predominantly in adipose tissue and linked to the adipose tissue expression of MMIF‐1

In this study, the regional adipose tissue‐adiponectin (AT‐ADN) and adiponectin receptor (R1 and R2) expression and their relation with metabolic parameters, circulating and AT‐derived cytokine expressions were compared. Paired subcutaneous adipose tissue (SCAT) and visceral adipose tissue (VAT) were taken from 18 lean and 39 obese humans, AT‐mRNA expression of adipokines analysed by RT‐PCR and corresponding serum levels by enzyme‐linked immunosorbent assay (ELISA). R1 and R2 adipocyte expression was compared with 17 other human tissues. ADN‐gene expression was lower in VAT than SCAT [mean (SD) 1.54 (1.1) vs. 2.84 (0.87); p < 0.001], and lower in obese subjects (VAT : p = 0.01;SCAT : p < 0.001). SCAT‐ADN correlated positively with serum ADN (r = 0.33;p = 0.036) but not VAT‐ADN. AT expressions of ADN and macrophage migration inhibiting factor (MMIF), IL18 and cluster of differentiation factor 14 (CD14) in both depots showed inverse correlations. R1 and R2 were expressed ubiquitously and R2 highest in SCAT, and this is much higher (×100) than R1 (×100). R expression was similar in lean and obese subjects and unrelated to the metabolic syndrome, however, receptors correlated with VAT‐MMIF (R 1: r = 0.4;p = 0.008;R 2: r = 0.35,p = 0.02) and SCAT‐MMIF expression (R 2: r = 0.43;p = 0.004). Unlike ADN, its receptors are expressed in many human tissues. Human R2 expression is not highest in the liver but in AT where it is associated with MMIF expression. The adiponectin‐dependent insulin‐sensitizing action of thiazolidinediones is thus probably to differ amongst species with weaker effects on the human liver.     

糖尿病和肥胖症患者网膜脂肪组织中的内脂素表达及其影响因素

目的探讨糖尿病、肥胖症患者网膜脂肪组织细胞内脂素的表达及其影响因素。方法选择糖尿病组、肥胖症组、健康对照组各60例,测定血清内脂素、脂联素、肿瘤坏死因子α（TNF-α）浓度。同时,选取三组共66例（糖尿病组23例、肥胖症组22例、对照组21例）行外科手术时切割的各内脏器官网膜脂肪组织提取总mRNA,然后进行Northern b lot印迹技术研究,分析内脂素mRNA差异表达以及与其他脂肪因子的相关关系。结果糖尿病和肥胖症患者血清内脂素浓度较对照组明显升高（P均〈0.01）,糖尿病、肥胖症血清内脂素浓度与TNF-α呈正相关（r=0.441,P=0.045;r=0.541,P=0.037）。网膜脂肪组织中内脂素mRNA的灰度值与血清内脂素、TNF-α水平呈正相关（r=0.771,P=0.021;r=0.500,P=0.041）。结论内脂素在2型糖尿病内脏脂肪及血清中高表达,TNF-α可能促进内脂素表达。     

Visceral, subcutaneous or intramuscular fat: where is the problem?

The adipose tissue is a dynamic organ that secrets several factors, denominated adipokines. They are associated, directly or indirectly, in a process that contributes to atherosclerosis, hypertension, insulinic resistance and diabetes type 2, dyslipidemias, presenting the link between adiposity, metabolic syndrome and cardiovascular diseases. In the obesity, body fat depots are increased, presenting eventual elevation in the adipokines expression and secretion. The different fat depots, visceral, abdominal subcutaneous, gluteal-femoral subcutaneous and intramuscular adipose tissue, have different metabolic and endocrine degrees, interfering, therefore, with specific form in the process associated with body adiposity in obese and diabetics subjects. The present study seeks to discuss the endocrine and metabolic role of each adipose tissue compartment, by way to assess their contribution to the complications linked to obesity.     

Relation of depot-specific adipose inflammation to insulin resistance in human obesity

BACKGROUND:

A low-grade state of adipose tissue inflammation associated with obesity has been linked to mechanisms of systemic metabolic dysfunction. However, the relation of clinical phenotypes to depot-specific inflammation has not been well examined in human obesity.

OBJECTIVE:

To characterize the inflammatory status of subcutaneous and visceral fat depots, as assessed by tissue presence of macrophage crown-like structures (CLS) as a hallmark of chronic inflammation, and determine the relation of systemic insulin resistance to inflammatory abnormalities in subcutaneous and visceral fat.

METHODS:

We collected adipose tissue simultaneously from subcutaneous and visceral (omental and mesenteric) depots in 92 obese participants (age 42±11 years; BMI⩾30 kg m⁻²) during planned bariatric surgery. Using immunohistochemistry, we categorized individuals as CLS⁺ or CLS⁻ based on the presence or absence, respectively, of macrophage CLS in subcutaneous (CLS_s), omental (CLS_o) and mesenteric (CLS_m) adipose depots.

RESULTS:

The majority of participants exhibited adipose tissue inflammation manifest by the presence of CLS (CLS⁺) in both subcutaneous and intra-abdominal visceral depots. CLS status in subcutaneous fat was highly sensitive and modestly specific for inflammation of visceral fat. In multivariable models, plasma insulin and homeostatis model assessment levels were positively associated with CLS⁺ status in all depots independent of age, waist circumference, BMI and type 2 diabetes, and worsened with the increasing number of adipose regions involved.

CONCLUSIONS:

In severely obese participants, systemic insulin resistance is linked to adipose inflammation in both subcutaneous and visceral depots. The findings suggest that examination of subcutaneous regions that are more easily accessible by transcutaneous biopsy may prove useful in clinical studies designed to investigate adipose phenotypes in relation to human disease.     

Fatty acid synthase gene expression in human adipose tissue: association with obesity and type 2 diabetes

Aims/hypothesis Increased expression and activity of the lipogenic pathways in adipose tissue may contribute to the development of obesity. As a central enzyme in lipogenesis, the gene encoding fatty acid synthase (FASN) was identified as a candidate gene for determining body fat. In the present study we tested the hypothesis that increased FASN expression links metabolic alterations of excess energy intake, including hyperinsulinaemia, dyslipidaemia and altered adipokine profile to increased body fat mass. Subjects and methods In paired samples of visceral and subcutaneous adipose tissue from 196 participants (lean or obese), we investigated whether FASN mRNA expression (assessed by PCR) in adipose tissue is increased in obesity and related to visceral fat accumulation, measures of insulin sensitivity (euglycaemic–hyperinsulinaemic clamp) and glucose metabolism. Results FASN mRNA expression was increased by 1.7-fold in visceral vs subcutaneous fat. Visceral adipose tissue FASN expression was correlated with FASN protein levels, subcutaneous FASN expression, visceral fat area, fasting plasma insulin, serum concentrations of IL-6, leptin and retinol-binding protein 4 (RBP4), and inversely with measures of insulin sensitivity, independently of age, sex and BMI. Moreover, we found significant correlations between FASN expression and markers of renal function, including serum creatinine and urinary albumin excretion. Conclusions/interpretation Increased FASN gene expression in adipose tissue is linked to visceral fat accumulation, impaired insulin sensitivity, increased circulating fasting insulin, IL-6, leptin and RBP4, suggesting an important role of lipogenic pathways in the causal relationship between consequences of excess energy intake and the development of obesity and type 2 diabetes.     

Association of cardiorespiratory fitness with insulin sensitivity in overweight and obese postmenopausal women: a Montreal Ottawa New Emerging Team study

The purpose of this study was to examine the relation between insulin sensitivity and cardiorespiratory fitness in overweight and obese postmenopausal women. The study population consisted of 127 overweight and obese postmenopausal women (age, 57.7 ± 4.8 years; body mass index, 32.7 ± 4.7 kg/m²). Subjects were classified by dividing the entire cohort into tertiles (T) based on insulin sensitivity expressed per kilograms of lean body mass (LBM) (T1, <10.9; T2, 10.9-12.9, T3, >12.9 mg/min per kilogram of LBM, respectively). Outcome measures were body composition (dual-energy x-ray absorptiometry), visceral adipose tissue (computed tomography), insulin sensitivity (hyperinsulinemic-euglycemic clamp), cardiorespiratory fitness (indirect calorimetry), lower-body muscle strength (1 maximal repetition), physical activity energy expenditure (doubly labeled water), fasting lipids, and inflammatory profile. We found a significant positive relationship between insulin sensitivity and cardiorespiratory fitness (r = 0.25, P = .005). Moreover, cardiorespiratory fitness was higher in the T3 group compared to the T1 group (36.2 ± 6.1 vs 33.1 ± 5.0 mL/kg LBM per minute, respectively; P = .028). However, the difference was no longer significant after controlling for visceral adipose tissue or muscle strength. Finally, cardiorespiratory fitness was an independent predictor of insulin sensitivity. High levels of cardiorespiratory fitness are associated with higher levels of insulin sensitivity in overweight and obese postmenopausal women. Moreover, visceral adipose tissue accumulation or muscle strength may be potential mediators of this relationship.     

Fat depot-specific expression of adiponectin is impaired in Zucker fatty rats

Adiposity, particularly increased intra-abdominal fat, is a predisposing factor for the development of insulin resistance in obesity and type 2 diabetes. Visceral fat seems to differ from subcutaneous adipose tissue in adipocytokine production. This fat depot-related difference has been viewed as an important mechanism by which adipose tissue exerts its paracrine/autocrine effects on peripheral tissue in modulating insulin sensitivity. We have studied the relative expression of adiponectin in visceral versus subcutaneous fat in Zucker fatty versus lean rats. Visceral fat, as opposed to subcutaneous fat, exhibited relatively higher levels of adiponectin production in lean animals. However, in Zucker fatty rats, adiponectin expression in visceral fat was suppressed to basal levels, which correlated with significantly reduced plasma adiponectin concentrations and increased insulin resistance. These results suggest that an impaired depot-specific expression of adiponectin is a contributing factor for the development of insulin resistance in Zucker fatty rats.     

Abdominal Obesity and Cardiovascular Disease: Is Inflammation the Missing Link?

It is well established that cardiovascular disease has an inflammatory component. The present narrative review explores the role of adipose tissue distribution, morphology, and function as potential mediators of the link between inflammation and cardiovascular disease. Evidence that abdominal obesity is a key driving force behind a constellation of atherothrombotic inflammatory abnormalities linked to insulin resistance and often referred to as the metabolic syndrome is also reviewed. It is also proposed that the amount of visceral adipose tissue and the liver fat content are important factors responsible for the link between abdominal obesity and features of the metabolic syndrome. It is suggested that the inflammatory profile associated with excess visceral adipose tissue/liver fat may be a consequence of the relative inability of subcutaneous adipose tissue to expand through hyperplasia and to act as a protective metabolic sink storing the chronic energy surplus resulting from a positive energy balance (overnutrition or lack of physical activity or both). In this model, the inflammatory profile often observed among sedentary overweight/obese individuals with an excess of visceral adipose tissue/liver fat may be a consequence of a more primary defect in subcutaneous adipose tissue. On that basis, it is proposed that therapeutic strategies relieving the stress for storage of a chronic energy surplus in the subcutaneous adipose tissue (reduced caloric intake, increase in energy expenditure, pharmacotherapy) should induce a substantial loss of visceral adipose tissue and of ectopic fat depots such as the liver, thereby substantially reducing inflammation.     

Increased systemic and adipose tissue inflammation differentiates obese women with T2DM from obese women with normal glucose tolerance

IntroductionObesity is strongly related to type-2 diabetes (T2DM), but there is a subset of obese individuals that remains relatively insulin sensitive and metabolically healthy. This study determined to what extent differences in metabolic health in obese women are associated with differences in adipose tissue and/or systemic inflammation.MethodsThe subject group consisted of age comparable lean (n = 12) and obese women either with T2DM (n = 28) or normal glucose tolerance (NGT; n = 26). Number of crown like structures (CLS) and adipocyte size were measured in subcutaneous and visceral adipose tissue of the obese women. Circulating cytokine and free fatty acid (FFA) levels, as well as number and activation status of peripheral leukocytes were determined.ResultsObese T2DM subjects showed higher circulating levels of IL-6, FFA and glycerol as compared to obese NGT subjects. Obese T2DM subjects had higher absolute numbers of peripheral leukocytes which were mainly due to an increase of T helper cells. Activation status of circulating cytotoxic T (CD8+CD25 +) and B (CD19+CD38 +) cells was significantly increased in obese NGT subjects as compared to lean but was not different between the two obese groups. Subcutaneous adipose tissue of obese T2DM subjects contained more CLS than adipose tissue of obese NGT subjects.ConclusionObese T2DM subjects show higher FFA levels and adipose tissue macrophage infiltration in addition to higher levels of circulating IL-6 and numbers of CD4 + T cells than obese NGT subjects. Hence, obese T2DM subjects show a higher extent of inflammation at both the systemic and adipose tissue level.     

Regional similarities in the metabolic regulation of adipose tissue lipoprotein lipase.

Seven normal weight and 10 obese women were studied to determine the relative activities of adipose tissue lipoprotein lipase (ATLPL) in the gluteal and abdominal subcutaneous adipose tissue depots, both in the fasting state and in response to a 6-hour insulin/glucose infusion. In normal weight women, fasting gluteal enzyme activity was greater than abdominal (P less than .02). In the obese group, fasting levels of ATLPL were higher in both the gluteal and abdominal depots than in the normal weight group, but similar between regions. The regulation of ATLPL by insulin/glucose was also similar between regions in each group. When both groups were considered together, there was a strong correlation between fasting ATLPL of both regions, and between the insulin responsiveness of gluteal ATLPL and abdominal ATLPL after a 6-hour infusion. Despite regional differences in fasting ATLPL in lean women, these studies indicate that the regulation of ATLPL by insulin/glucose is largely similar in at least these two subcutaneous adipose tissue depots.