Contribution Of Visceral Adipose Tissue Research Articles

Profiling hypertrophic adipocytes in humans, from transcriptomics to diagnostics.

Obesity rates continue to rise worldwide, with a concomitant increase in co-morbidities, including metabolic disease, cardiovascular disease and cancer. The onset of obesity is most often characterized by an increase in the size of white adipose tissue fat cells (adipocyte hypertrophy) and secondary to this by adipocyte hyperplasia. Adipocyte hypertrophy is strongly linked to metabolic and cardiovascular disease with hypertrophy and not obesity per se, a predictor of type 2 diabetes.1 The contribution of visceral adipose tissue to these pathologies is even more pronounced.

Arterial stiffness in patients with chronic heart failure: the role of visceral obesity

Abstract Background Chronic heart failure (CHF) and obesity have a negative impact on the target organs, including the condition of blood vessels. This is manifested in a progressive decrease of the elasticity of the main arteries. Objective To evaluate the effect of visceral obesity on the condition of the main arteries in patients with CHF. Methods The study included 116 patients with CHF of functional class I-III of ischemic genesis aged from 40 to 65 years, who were divided into 3 comparable groups: group 1 included patients with CHF with normal body weight (n=34), group 2 - overweight CHF (n=40), group 3 – CHF and grade 1–2 obesity (n=42). There were no differences in the severity of CHF between the study groups. The examination included an assessment of the general condition, anthropometry with measurement of the waist circumference (WC), hip circumference (HC), the ratio of WC/HC, as well as bioimpedansmetry with an assessment of the content of subcutaneous and visceral fat in the body. The visceral fat index (VAI) was calculated. Arterial stiffness was assessed by measuring the pulse wave velocity (PWV). The results were processed using the built - in functions of the MC Excel program and the STATISTICA 12.0 program. Results A significant increase in the ratio of WC/HC in patients of the 2nd and 3rd groups compared to patients of the 1st group was determined. Abdominal obesity was significantly more common among overweight and obese patients compared to those with normal body weight (78.6, 70, and 0%). A high percentage of visceral obesity was found among people with concomitant obesity/overweight: in 70% among overweight individuals and in 100% among obese individuals. The VAI was higher among patients with CHF and obese/CHF and overweight compared to those with “isolated” CHF. Differences were found in the average thickness of epicardial adipose tissue (EAT), which is a marker of visceral obesity. There was a statistically significant increase in PWV in elastic vessels (PWVe) in patients with CHF and obesity compared to patients with CHF and normal body weight (10.5 [8.9; 11.6] m/s vs 8.5 [7.5; 8.4] m/s. PWVe>10 m/s was significantly more common among over weight or obese patients compared to patients with normal body weight (62.4 and 83.2% vs 37.5%, respectively). Significant correlations were found between PWVe and the severity of visceral obesity (r=0.53, p<0.05), PWVe and WC (r=0.56, p<0.05), PWVe and WC/HC (r=0.48, p<0.05). PWVe was positively correlated witht EAT (r=0.36, p<0.05) and VAI (r=0.34, p<0.05). Conclusion The combination of CHF with obesity negatively affects the condition of the main arteries. The relationship between the parameters characterizing the elasticity of the vascular wall and the severity of visceral obesity reflects the important pathogenetic contribution of visceral adipose tissue to the development and progression of arterial stiffness in patients with CHF and obesity. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Grant of Federal State Budgetary Educational Institution of Higher Education “The Volgograd State Medical University” of the Ministry of Health of the Russian Federation

Circulating phospholipid profiling identifies portal contribution to NASH signature in obesity

Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, hepatocyte ballooning with fibrosis in severe cases, and high prevalence in obesity. We aimed at defining NASH signature in morbid obesity by mass spectrometry-based lipidomic analysis. We analyzed systemic blood before and 12 months after bariatric surgery, along with portal blood and adipose tissue lipid efflux collected from obese women at the time of surgery (9 structural classes, 150 species). Increased concentrations of several glycerophosphocholines (PC), glycerophosphoethanolamines (PE), glycerophosphoinositols (PI), glycerophosphoglycerols (PG), lyso-glycerophosphocholines (LPC), and ceramides (Cer) were detected in systemic circulation of NASH subjects. Post-surgery weight loss (12 months) improved the levels of liver enzymes, as well as several lipids, but most PG and Cer species remained elevated. Analysis of lipids from hepatic portal system at the time of surgery revealed limited lipid alterations compared to systemic circulation, but PG and PE classes were found significantly increased in NASH subjects. We evaluated the contribution of visceral adipose tissue to lipid alterations in portal circulation by measuring adipose tissue lipid efflux ex vivo, and observed only minor alterations in NASH subjects. Interestingly, integration of clinical and lipidomic data (portal and systemic) led us to define a NASH signature in which lipids and clinical parameters are equal contributors. Circulatory (portal and systemic) phospholipid profiling and clinical data defines NASH signature in morbid obesity. We report weak contribution of visceral adipose tissue to NASH-related portal lipid alterations, suggesting possible contribution from other organs draining into hepatic portal system.

Ectopic Fat Deposition in Prediabetic Overweight and Obese Minority Adolescents

Optimizing effective prevention and treatment of type 2 diabetes in youth is limited by incomplete understanding of its pathophysiology and how this varies across ethnicities with high risk. The aim of this study was to examine the contribution of visceral adipose tissue (VAT), hepatic fat fraction (HFF), and pancreatic fat fraction (PFF) to prediabetes in overweight/obese African American (AA) and Latino youth. We conducted a cross-sectional study in an academic pediatric care facility. A total of 148 healthy, overweight/obese adolescents (56 AA, 92 Latino; 72 males, 76 females; age, 15.5 ± 1.2 y; BMI z-score, 2.1 ± 0.5) participated in the study. They were normal glucose tolerant (n = 106) and prediabetic (n = 42), based on fasting glucose of 100-125 mg/dL and/or 2-hour glucose of 140-199 mg/dL, and/or hemoglobin A1C 6.0-6.4%. We measured sc abdominal adipose tissue, VAT, HFF, and PFF by 3-Tesla magnetic resonance imaging and measured total body fat by dual-energy x-ray absorptiometry. Adolescents with prediabetes had 30% higher HFF (P = .001) and 31% higher PFF (P = .042), compared to those with normal glucose tolerance after controlling for age, sex, pubertal stage, ethnicity, total percentage body fat, and VAT. Logistic regression showed that PFF predicted prediabetes in AAs and HFF predicted prediabetes in Latinos, with the odds of having prediabetes increased by 66% for every 1% increase in PFF in African Americans, and increased by 22% for every 1% increase in HFF in Latinos. These data demonstrate that ectopic fat phenotypes associated with prediabetes are established by adolescence. Ethnic differences in the deposition of ectopic fat in adolescents with prediabetes may differ, with pancreatic fat in AAs, vs hepatic fat in Latino adolescents, being associated with diabetes risk.

Associations between circulating free fatty acids, visceral adipose tissue accumulation, and insulin sensitivity in postmenopausal women

The aims of the study were to evaluate the contribution of visceral adipose tissue (AT) accumulation and insulin sensitivity to the determination of circulating free fatty acid (FFA) concentrations measured during a 2-hour euglycemic-hyperinsulinemic clamp and to verify whether elevated FFAs are associated with other components of the metabolic syndrome in postmenopausal women. This cross-sectional study included 115 postmenopausal women (46-68 years old). Visceral AT was estimated by computed tomography. Insulin sensitivity was assessed by a 2-hour euglycemic-hyperinsulinemic clamp. Free fatty acid concentration was measured in the fasting state and every 30 minutes during the clamp. Fasting plasma glucose and 2-hour plasma glucose were measured by an oral glucose tolerance test. Visceral AT was associated positively and insulin sensitivity negatively with FFA area under the curve (AUC) measured during the clamp. Women with high visceral AT accumulation and low insulin sensitivity had higher FFA AUC than women with high visceral AT accumulation and high insulin sensitivity or women with low visceral AT combined with either low or high insulin sensitivity. Free fatty acid AUC was positively associated with triglyceride (r = 0.25, P < .05), fasting plasma glucose (r = 0.26, P < .01), 2-hour plasma glucose (r = 0.27, P < .01), and diastolic blood pressure (r = 0.21, P < .05) independently of visceral AT and insulin sensitivity. In postmenopausal women, the presence of both high visceral AT and low insulin sensitivity is needed to observe an elevated FFA AUC. Moreover, FFA AUC is associated with some components of the metabolic syndrome, independently of visceral AT and insulin sensitivity.

Increased plasma interleukin-1 receptor antagonist levels in men with visceral obesity

Background. Adipose tissue (AT) is an important source of interleukin-1 receptor antagonist (IL-1Ra). Its expression is markedly increased in obesity.Aims and methods. To quantify the associations of IL-1Ra with body fat distribution as well as to examine the respective contributions of IL-1Ra and visceral adiposity to the variation in some cardiometabolic risk (CMR) markers. Plasma IL-1Ra levels were measured in a sample of 117 healthy non-diabetic men (age: 44.9±10.1 years; body mass index (BMI): 28.8±4.5 kg/m2).Results. Plasma IL-1Ra levels correlated positively with BMI, waist girth, and visceral and subcutaneous AT (0.39 ≤ r<0.48; P < 0.0001). Multiple regression analyses revealed that visceral AT was the best independent predictor of IL-1Ra levels, explaining 22% (P < 0.0001) of its variance. IL-1Ra (P < 0.05) was an independent predictor of several CMR markers including triglyceride and high-density lipoprotein (HDL) cholesterol levels, cholesterol/HDL cholesterol ratio, glucose and insulin concentrations in response to a 75 g oral glucose load, and fasting insulin levels, in addition to the expected contribution of visceral AT (P < 0.05).Conclusions. These results suggest that elevated IL-1Ra concentrations are influenced to a greater extent by visceral than subcutaneous adiposity and that IL-1Ra is independently related to some features of CMR beyond the known contribution of visceral adiposity.

The contribution of omental adipose tissue to adipokine concentrations in patients with the metabolic syndrome

To examine differences in peripheral vascular endothelial growth factor (VEGF), interleukin-6 (IL6) and cortisol concentrations between patients with both visceral obesity and metabolic syndrome, and lean controls. In a subsample of metabolic patients underwent abdominal surgery, the adipokine concentrations were measured in venous blood from the omentum to determine information on some processes of synthesis. Forty-two healthy lean controls and 46 overweight-obese patients with central adiposity and stigmata of metabolic syndrome were studied. In a subsample of 11 metabolic patients undergoing non-bariatric surgery, blood samples from omental and peripheral veins were taken intraoperatively to determine VEGF, IL6 and cortisol concentrations. Median levels (range) of peripheral VEGF and IL6 were higher in patients than in controls [31.5 (3-112) pg/mL vs 21.35 (9-41.9) pg/mL (P < 0.05) and 5.50 (1.40-13) pg/mL vs 1.15 (0.3-1) pg/mL (P < 0.0001)]. On the other hand, concentrations of VEGF and IL6 from the omental and peripheral veins were similar in the surgery sub-group. Peripheral cortisol concentrations were not higher in patients than in controls, nor were omental concentrations different from the peripheral. Omental and peripheral VEGF and cortisol values were correlated, whereas no association was found between omental and peripheral IL6. In the presence of abdominal obesity, VEGF and IL6 concentrations are increased in the systemic circulation. The contribution of visceral adipose tissue to circulating levels of VEGF and IL6 was modest.

Regional Fat Deposition as a Factor in FFA Metabolism

Humans have a large variability in body fat distribution, which has tremendous implications for metabolic health. Obese individuals with an upper-body-fat distribution have increased health complications such as dyslipidemia, hypertension, insulin resistance, and type 2 diabetes in comparison with lower-body-obese individuals. Additionally, females have more body fat, a greater proportion of fat in their lower body, and much less visceral fat than do lean males at the same body mass index. The reasons for these differences in body fat distribution have not been clearly identified but could be important. Herein we review what has been learned about regional differences in triglyceride storage capacity and lipolysis as they relate to the causes and consequences of regional fat accumulation. Both sex and site differences in regional fat storage have been described. In contrast, with the exception of variations between men and women in the contribution of visceral adipose tissue to hepatic FFA delivery, most studies have failed to show important sex differences in regional lipolysis in vivo.

Abstract 4189: Gender Difference in Inflammatory Markers: What is the Contribution of Visceral Adiposity?

Several studies have reported a gender difference in inflammatory markers associated with obesity. Indeed, whereas C-reactive protein (CRP) concentrations have been found to be higher in pre-menopausal women compared to men, interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels have been found to be lower in women than in men because of the inhibitory effect of estrogens on the expression of inflammatory genes. Since body fat distribution is very different between men and pre-menopausal women, the contribution of visceral adipose tissue (VAT) to the gender difference in inflammatory markers is a question of clinical relevance. To examine this issue, plasma CRP, IL-6 and TNF-α levels were measured in a sample of 195 healthy men (age: 41.7±14.9 years) and 139 healthy women (age: 36.6±11.2 years). Pre-menopausal women were characterized by lower plasma TNF-α levels (1.57±0.59 pg/mL vs.1.85±0.99 pg/mL, p=0.001) and higher CRP concentrations (1.91±1.77 mg/L vs. 1.65±1.78 mg/L, p=0.04) than men whereas the IL-6 levels did not differ between genders. Significant positive relationships were observed between VAT accumulation and CRP concentrations in men (r=0.43, p&lt;0.0001) and in women (r=0.42, p&lt;0.0001), or IL-6 in men (r=0.42, p&lt;0.0001) and in women (r=0.51, p&lt;0.0001). Regression analyses showed that gender did affect the associations between VAT and CRP. In order to investigate the contribution of visceral adiposity to the gender variation in inflammatory markers, 85 men and 85 pre-menopausal women were individually matched on the basis of similar VAT accumulation. After such matching procedure, women still had significantly higher CRP levels than men (2.07±1.88 and 1.57±1.84 mg/L, p=.01) whereas no differences were observed in IL-6 and TNF-α concentrations. Thus, these results suggest that the gender difference in CRP levels is not entirely explained by the greater amount of VAT generally observed in men.

The Contribution of Visceral Adipose Tissue to Splanchnic Cortisol Production in Healthy Humans

Cortisol is regenerated from cortisone by 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1), amplifying glucocorticoid action in adipose tissue and liver. 11HSD1 inhibitors are being developed for type 2 diabetes and may be most effective in obesity, where adipose 11HSD1 is increased. However, the magnitude of regeneration of cortisol in different tissues in humans is unknown, hindering understanding of the pathophysiological and therapeutic importance of 11HSD1. In eight healthy men, we infused 9,11,12,12-(2)H4-cortisol and measured tracer enrichment in the hepatic vein as an indicator of total splanchnic cortisol generation. Oral cortisone (25 mg) was then given to measure first-pass hepatic cortisol generation. In steady state, splanchnic cortisol production was 45 +/- 11 nmol/min when arterialized plasma cortisone concentration was 92 +/- 7 nmol/l. Extrapolation from hepatic cortisol generation after oral cortisone suggested that, at steady state, the liver contributes 15.2 nmol/min and extrahepatic splanchnic tissue contributes 29.8 nmol/min to the total splanchnic cortisol production. We conclude that tissues draining into the portal vein, including visceral adipose tissue, contribute substantially to the regeneration of cortisol. Thus, in addition to free fatty acids and adipokines, the portal vein delivers cortisol to the liver, and inhibition of 11HSD1 in visceral adipose tissue may indeed be valuable in ameliorating insulin resistance in obesity.

Associations between the fatty acid content of triglyceride, visceral adipose tissue accumulation, and components of the insulin resistance syndrome

Many factors are involved in the development of the insulin resistance syndrome, such as visceral obesity and the type of dietary fat. The main purpose of this study was to investigate the relationships between fatty acid content of triglyceride (TG), visceral adipose tissue (AT) accumulation, and metabolic components of the insulin resistance syndrome in a group of 97 Caucasian men with a mean age of 45.1 ± 7.2 years (29 to 63 years). To reach these objectives, Spearman correlations, group comparisons, and stepwise multiple regression analyses were performed. The proportion of palmitic acid (16:0) in the TG fraction was positively associated with plasma fasting insulin ( r = .25, P = .03), diastolic ( r = .45, P <.001), and systolic ( r = .29, P = .003) blood pressure. On the other hand, the proportion of α-linolenic acid (18:3n-3) was associated negatively with apolipoprotein (apo) B ( r = −.29, P = .005) and positively with low-density lipoprotein (LDL) diameter ( r = .29, P = .007), while the proportion of γ-linolenic acid (18:3n-6) was associated negatively with plasma TG ( r = −.33, P = .003), diastolic ( r = −.29, P = .01), and systolic ( r = −.35, P = .002) blood pressure and plasma fasting insulin ( r = −.37, P = .0005) and positively with high-density lipoprotein (HDL) 2-cholesterol ( r = .27, P = .01) and LDL diameter ( r = .25, P = .02). Stepwise multiple regression analyses were conducted to determine the contribution of visceral AT, body fat mass, and the fatty acid content of TG to the variance of metabolic variables studied. It was found that visceral AT contributed significantly to the variance in plasma TG ( R 2 = 20.7%, P <.0001), apo B ( R 2 = 9.0%, P = .007), HDL 2-cholesterol ( R 2 = 17.9%, P <.0001), LDL diameter ( R 2 = 4.9%, P = .02), and area under the glucose curve (AUC-glucose) ( R 2 = 8.2%, P = .006). On the other hand, body fat mass contributed significantly to the variance in fasting insulin ( R 2 = 19.7%, P <.0001) and diastolic ( R 2 = 6.8%, P = .007) and systolic ( R 2 = 10.5%, P = .01) blood pressure. At least one fatty acid made a significant contribution to the variance of each metabolic variable studied. In fact, the proportion of 18:3n-6 contributed significantly to the variance in both TG ( R 2 = 8.9%, P = 0.007) and HDL 2-cholesterol ( R 2 = 6.0%, P = .01). Moreover, 18:3n-3 contributed to the variance of apo B ( R 2 = 7.0%, P = .02), while 18:3n-6 made the largest contribution to the variance of LDL diameter ( R 2 = 7.6%, P = .02). Finally, 16:0 significantly contributed to the variance of AUC-glucose ( R 2 = 11.4%, P = .0003), diastolic ( R 2 = 25.2%, P <.0001), and systolic ( R 2 = 6.8%, P = .002) blood pressure. In summary, results of this study suggest that the fatty acid content of TG is associated with many metabolic variables of the insulin resistance syndrome independently of body fat mass or visceral AT accumulation.

Deterioration of the metabolic risk profile in women. Respective contributions of impaired glucose tolerance and visceral fat accumulation.

To determine whether the impaired glucose tolerance (IGT) state contributes to the deterioration of the metabolic profile in women after taking into account the contribution of visceral adipose tissue (AT) accumulation, as measured by computed tomography. We studied 203 women with normal glucose tolerance (NGT) and 46 women with IGT, defined as a glycemia between 7.8 and 11.1 mmol/l measured 2 h after a 75-g oral glucose load. Women with IGT were characterized by a higher visceral AT accumulation and by higher concentrations of fasting plasma glucose, insulin, and C-peptide as well as by higher plasma concentrations of cholesterol, triglycerides, and apolipoprotein B (apoB) and by greater cholesterol-to-HDL-cholesterol ratio, reduced LDL peak particle size, lower HDL-cholesterol and HDL2-cholesterol concentrations, and higher blood pressure (P < 0.01) than women with NGT. When we matched 27 pairs of women for visceral AT and fat mass as well as for menopausal status, differences previously found in LDL-cholesterol, LDL peak particle size, HDL-cholesterol, and HDL2-cholesterol concentrations as well as in the cholesterol-to-HDL-cholesterol ratio and blood pressure were eliminated, whereas triglyceride concentrations remained significantly higher in women with IGT. A high visceral AT accumulation is a major factor involved in the deterioration of many metabolic variables in women with IGT, with the notable exception of triglyceride concentrations, which remained significantly different between women with NGT and women with IGT after adjustment for visceral fat.