Visceral fat and liver fat are independent predictors of metabolic risk factors in men

We examined the independent associations among abdominal adipose tissue (AT), liver fat, cardiorespiratory fitness (CRF), and lipid variables in 161 Caucasian men who had a wide variation in adiposity. We measured AT and liver fat by computed tomography and CRF by a maximal exercise test on a treadmill. Visceral AT remained a significant (P or= 0.05) correlate of any lipid variable after control for visceral AT and CRF. Furthermore, subdivision of subcutaneous AT into deep and superficial depots did not alter these observations. Visceral AT was the strongest correlate of liver fat and remained so after control for abdominal subcutaneous AT, CRF, and alcohol consumption (r = -0.34, P < 0.01). In contrast, abdominal subcutaneous AT and CRF were not significant (P > 0.10) correlates of liver fat after control for visceral AT. Visceral AT remained a significant (P < 0.01) correlate of TG, HDL-C, and TC/HDL-C independent of liver fat. However, liver fat was also a significant correlate (P 相似文献   

Depot-Specific Changes in Fat Metabolism with Aging in a Type 2 Diabetic Animal Model

Visceral fat accretion is a hallmark of aging and is associated with aging-induced metabolic dysfunction. PPARγ agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARγ activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARγ agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARγ agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation.     

Topical application of capsaicin reduces visceral adipose fat by affecting adipokine levels in high‐fat diet‐induced obese mice

Objective:

Visceral obesity contributes to the development of obesity‐related disorders such as diabetes, hyperlipidemia, and fatty liver disease, as well as cardiovascular diseases. In this study, we determined whether topical application of capsaicin can reduce fat accumulation in visceral adipose tissues.

Methods and Results:

We first observed that topical application of 0.075% capsaicin to male mice fed a high‐fat diet significantly reduced weight gain and visceral fat. Fat cells were markedly smaller in the mesenteric and epididymal adipose tissues of mice treated with capsaicin cream. The capsaicin treatment also lowered serum levels of fasting glucose, total cholesterol, and triglycerides. Immunoblot analysis and RT‐PCR revealed increased expression of adiponectin and other adipokines including peroxisome proliferator‐activated receptor (PPAR) α, PPARγ, visfatin, and adipsin, but reduced expression of tumor necrosis factor‐α and IL‐6.

Conclusions:

These results indicate that topical application of capsaicin to obese mice limits fat accumulation in adipose tissues and may reduce inflammation and increase insulin sensitivity.     

Frequency of non-alcoholic fatty liver disease in overweight/obese children and adults: Clinical,sonographic picture and biochemical assessment

Non-alcoholic fatty liver disease (NAFLD) is a condition defined by significant lipid accumulation (5–10%) in hepatic tissue in the absence of significant chronic alcohol consumption. We aim to detect frequency of fatty liver among overweight/obese adults and children and associated clinical; anthropological measures; biochemical; genetic and imaging studies. Eighty three consecutive adults and 72 children included in the study. All patients underwent clinical measurements of height, body weight, body mass index (BMI), waist and hip circumference. Biochemical investigations were done to all subjects including liver function tests; lipid profile; fasting blood glucose; insulin resistance (IR); high sensitivity C reactive protein (hs-CRP); adiponectin and genotyping of adiponectin genes. Abdominal ultrasonography was done to search for fatty liver; to measure subcutaneous fat thickness (SFT) and visceral fat thickness (VFT). Fatty liver was detected in 47 (65.3%) children and in 52 (62.7%) adults. Correlation analysis in both groups revealed that enlarged liver was highly positively correlated to age; BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP); waist circumference; hip circumference, subcutaneous fat thickness (SFT) and Visceral fat thickness (VFT), alanine aminotransferase (ALT), aspartate aminotransferase/alanine aminotransferase (AST/ALT). In addition in adults to fasting blood glucose, cholesterol, triglycerides (TG), low density lipoprotein (LDL), IR and hs-CRP. Homozygous T adiponectin genotype at position +276 was significantly increased among children with enlarged liver size and hs-CRP. NAFLD affects a substantial portion of adults and children; it is associated with the metabolic syndrome.     

Carbenoxolone alters the morphology of adipose tissues and downregulates genes involved in adipogenesis, glucose transport and lipid metabolism in high-fat diet-fed mice

Glucocorticoid (GC) excess promotes adipose tissue accumulation, and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays an important role in the local amplification of GC. Therefore, in this study, we investigated the effects of carbenoxolone (CBX), an 11β-HSD1 inhibitor, on morphological changes in visceral fat, and the expression of genes involved in adipogenesis and lipid metabolism in high-fat (HF) diet-fed mice. Mice were fed a HF diet from 5 weeks of age. At 10 weeks of age, the mice received an intraperitoneal injection of CBX or vehicle every day for 2 weeks. CBX decreased body weight and visceral fat mass, and improved insulin sensitivity in HF-fed mice. This was accompanied by reduced adipocyte size and a decrease in large-sized adipocytes in visceral fat. The expression of adipogenesis (PPARγ and C/EBPα), glucose transport (GLUT4) and lipid metabolism (LPL, ATGL, and HSL)-related genes were suppressed in CBX mice. CBX treatment induced beneficial morphological changes in visceral fat and decreased the expression of adipogenesis, glucose transport and lipid metabolism-related genes. These findings reveal a potential mechanism underling the effects of CBX on reduced fat accumulation and improved insulin sensitivity.     

Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine

We studied the effect of dietary fat type, varying in polyunsaturated-to-saturated fatty acid ratios (P/S), on development of metabolic syndrome. C57Bl/6J mice were fed purified high-fat diets (45E% fat) containing palm oil (HF-PO; P/S 0.4), olive oil (HF-OO; P/S 1.1), or safflower oil (HF-SO; P/S 7.8) for 8 wk. A low-fat palm oil diet (LF-PO; 10E% fat) was used as a reference. Additionally, we analyzed diet-induced changes in gut microbiota composition and mucosal gene expression. The HF-PO diet induced a higher body weight gain and liver triglyceride content compared with the HF-OO, HF-SO, or LF-PO diet. In the intestine, the HF-PO diet reduced microbial diversity and increased the Firmicutes-to-Bacteroidetes ratio. Although this fits a typical obesity profile, our data clearly indicate that an overflow of the HF-PO diet to the distal intestine, rather than obesity itself, is the main trigger for these gut microbiota changes. A HF-PO diet-induced elevation of lipid metabolism-related genes in the distal small intestine confirmed the overflow of palm oil to the distal intestine. Some of these lipid metabolism-related genes were previously already associated with the metabolic syndrome. In conclusion, our data indicate that saturated fat (HF-PO) has a more stimulatory effect on weight gain and hepatic lipid accumulation than unsaturated fat (HF-OO and HF-SO). The overflow of fat to the distal intestine on the HF-PO diet induced changes in gut microbiota composition and mucosal gene expression. We speculate that both are directly or indirectly contributive to the saturated fat-induced development of obesity and hepatic steatosis.     

Differential gene expression between visceral and subcutaneous fat depots.

Abdominal obesity has been linked to the development of insulin resistance and Type 2 diabetes mellitus (DM2). By surgical removal of visceral fat (VF) in a variety of rodent models, we prevented insulin resistance and glucose intolerance, establishing a cause-effect relationship between VF and the metabolic syndrome. To characterize the biological differences between visceral and peripheral fat depots, we obtained perirenal visceral (VF) and subcutaneous (SC) fat from 5 young rats. We extracted mRNA from the fat tissue and performed gene array hybridization using Affymetrix technology with a platform containing 9 000 genes. Out of the 1 660 genes that were expressed in fat tissue, 297 (17.9 %) genes show a two-fold or higher difference in their expression between the two tissues. We present the 20 genes whose expression is higher in VF fat (by 3 - 7 fold) and the 20 genes whose expression is higher in SC fat (by 3 - 150 fold), many of which are predominantly involved in glucose homeostasis, insulin action, and lipid metabolism. We confirmed the findings of gene array expression and quantified the changes in expression in VF of genes involved in insulin resistance (PPARgamma leptin) and its syndrome (angiotensinogen and plasminogen activating inhibitor-1, PAI-1) by real-time PCR (qRT-PCR) technology. Finally, we demonstrated increased expression of resistin in VF by around 12-fold and adiponectin by around 4-fold, peptides that were not part of the gene expression platform. These results indicate that visceral fat and subcutaneous fat are biologically distinct.     

Diabetogenic diet-induced insulin resistance associates with lipid droplet proteins and adipose tissue secretome,but not with sexual dimorphic adipose tissue fat accumulation in Wistar rats

The role of sexual dimorphic adipose tissue fat accumulation in the development of insulin resistance is well known. However, whether vitamin A status and/or its metabolic pathway display any sex- or depot (visceral/subcutaneous)-specific pattern and have a role in sexual dimorphic adipose tissue development and insulin resistance are not completely understood. Therefore, to assess this, 5 weeks old Wistar male and female rats of eight from each sex were provided either control or diabetogenic (high fat, high sucrose) diet for 26 weeks. At the end, consumption of diabetogenic diet increased the visceral fat depots (p < 0.001) in the males and subcutaneous depot (p < 0.05) in the female rats, compared to their sex-matched controls. On the other hand, it caused adipocyte hypertrophy (p < 0.05) of visceral depot (retroperitoneal) in the females and subcutaneous depot of the male rats. Although vitamin A levels displayed sex- and depot-specific increase due to the consumption of diabetogenic diet, the expression of most of its metabolic pathway genes in adipose depots remained unaltered. However, the mRNA levels of some of lipid droplet proteins (perilipins) and adipose tissue secretory proteins (interleukins, lipocalin-2) did display sexual dimorphism. Nonetheless, the long-term feeding of diabetogenic diet impaired the insulin sensitivity, thus affected glucose clearance rate and muscle glucose-uptake in both the sexes of rats. In conclusion, the chronic consumption of diabetogenic diet caused insulin resistance in the male and female rats, but did not corroborate with sexual dimorphic adipose tissue fat accumulation or its vitamin A status.     

Roles of degree of fat deposition and its localization on VEGF expression in adipocytes

Vascular endothelial growth factor (VEGF) is an important angiogenic factor and is expressed in wide variety of cell types. In this study, we investigated the mechanism of VEGF production in adipocytes in three sets of experiments. First, to clarify the relation between plasma VEGF concentrations and their expressions in adipose tissues, we investigated the genetically obese db/db and KK-Ay mice. Plasma VEGF concentrations in obese mice were significantly higher than in control and were related to adiposity. VEGF expressions in visceral fat were enhanced during growth and were related to fat deposition. Next, to demonstrate the relation between VEGF production and lipid accumulation in adipocytes, we analyzed VEGF mRNA expression and its protein secretion in 3T3-L1 cells. VEGF production was enhanced during lipid accumulation in 3T3-L1 cells after adipocyte conversion. Next, to clarify the role of anatomic localization on VEGF expression in adipocytes, we implanted 3T3-L1 cells into visceral or subcutaneous fat in athymic mice. 3T3-L1 cells implanted into the mesenteric area expressed more VEGF mRNA than that into the subcutaneous area. Plasma VEGF concentration in the mice implanted in visceral fat was higher than in controls. These results suggest that both the anatomic localization and the lipid accumulation are important for the VEGF production in adipocytes.     

Ethnic differences in lipid metabolism in two groups of obese South African women

There is a higher prevalence of ischemic heart disease (IHD) in South African white than black women. The objective of this study was to determine biochemical explanations for this prevalence. The study group contained 15 obese black women (OBW) and 14 obese white women (OWW), all premenopausal, who were examined after an overnight fast. Anthropometric measurements and blood concentrations of glucose, non-esterified fatty acids (NEFAs), catecholamines, plasminogen activator inhibitor-1, C-peptide, proinsulin, lipograms, cortisol, growth hormone, and post-heparin lipoprotein lipase activity were measured during an oral glucose tolerance test (OGTT). Body composition was measured using bioelectrical impedance analysis, and subcutaneous and visceral fat mass were assessed with CT-scans. Visceral fat area was higher in OWW (139.7 +/- 10.7 cm(2)) than in OBW (72.3 +/- 3.9 cm(2)) (P < 0.01), as were fasting and 3 h triglyceride concentrations (P < 0.05 for all). OWW also had higher NEFA levels than OBW at 3 and 4 h compared with OBW (P < 0.05 for both). Fasting cortisol (266 +/- 24 vs. 197 +/- 19 nmol/l; P < 0.05) was higher in OWW than in OBW.These data demonstrate that OWW have higher visceral fat mass than OBW, which may lead to a more atherogenic fasting and postprandial lipid profile. The higher cortisol levels of the OWW may promote visceral fat deposition.     

Dose-dependent effects of dietary fat on development of obesity in relation to intestinal differential gene expression in C57BL/6J mice

Excessive intake of dietary fat is known to be a contributing factor in the development of obesity. In this study, we determined the dose-dependent effects of dietary fat on the development of this metabolic condition with a focus on changes in gene expression in the small intestine. C57BL/6J mice were fed diets with either 10, 20, 30 or 45 energy% (E%) derived from fat for four weeks (n = 10 mice/diet). We found a significant higher weight gain in mice fed the 30E% and 45E% fat diet compared to mice on the control diet. These data indicate that the main shift towards an obese phenotype lies between a 20E% and 30E% dietary fat intake. Analysis of differential gene expression in the small intestine showed a fat-dose dependent gradient in differentially expressed genes, with the highest numbers in mice fed the 45E% fat diet. The main shift in fat-induced differential gene expression was found between the 30E% and 45E% fat diet. Furthermore, approximately 70% of the differentially expressed genes were changed in a fat-dose dependent manner. Many of these genes were involved in lipid metabolism-related processes and were already differentially expressed on a 30E% fat diet. Taken together, we conclude that up to 20E% of dietary fat, the small intestine has an effective ‘buffer capacity’ for fat handling. From 30E% of dietary fat, a switch towards an obese phenotype is triggered. We further speculate that especially fat-dose dependently changed lipid metabolism-related genes are involved in development of obesity.     

Vaspin gene in rat adipose tissue: relation to obesity-induced insulin resistance

Visceral adipose fat has been claimed to be the link between obesity and insulin resistance through the released adipokines. This study aimed to assess the expression of vaspin as one of the recent adipokines in rats abdominal subcutaneous and visceral fat in diet-induced obese (DIO) and in DIO performing 3 weeks swimming exercise (DIO + EXE) compared to control and control + exercise (C + EXE) groups. Vaspin mRNA and protein expression assessed using RT-PCR and Western blotting analysis revealed vaspin expression in DIO and DIO + EXE but not in controls groups. In DIO group, visceral vaspin expression was higher than in that of subcutaneous fat and was positively correlated with body weight. Upregulation of visceral vaspin expression in DIO was concomitant with the development of insulin resistance (increase in fasting serum insulin and HOMA-IR) and rise in serum leptin level. Unchanged visceral vaspin mRNA in DIO + EXE rats, with significant improvements of insulin resistance parameters and serum leptin compared to DIO group was found. In conclusion, increased visceral vaspin expression in obesity was associated with insulin resistance. Further investigations into the molecular links between vaspin and obesity may unravel innovative therapeutic strategies in people affected by obesity-linked insulin resistance, metabolic syndrome, and type 2 diabetes.     

Depot-specific regulation of autotaxin with obesity in human adipose tissue

Autotaxin (ATX) is a lysophospholipase D involved in synthesis of a bioactive mediator: lysophosphatidic. ATX is abundantly produced by adipocytes and exerts a negative action on adipose tissue expansion. In both mice and humans, ATX expression increases with obesity in association with insulin resistance. In the present study, fat depot-specific regulation of ATX was explored in human. ATX mRNA expression was quantified in visceral and subcutaneous adipose tissue in obese (BMI?>?40?kg/m²; n?=?27) and non-obese patients (BMI?<?25?kg/m²; n?=?10). Whatever the weight status of the patients is, ATX expression was always higher (1.3- to 6-fold) in subcutaneous than in visceral fat. Nevertheless, visceral fat ATX was significantly higher (42?%) in obese than in non-obese patients, whereas subcutaneous fat ATX remained unchanged. In obese patients, visceral fat ATX expression was positively correlated with diastolic arterial blood pressure (r?=?0.67; P?=?0.001). This correlation was not observed with subcutaneous fat ATX. Visceral fat ATX was mainly correlated with leptin (r?=?0.60; P?=?0.001), inducible nitric oxide synthase (r?=?0.58; P?=?0,007), and apelin receptor (r?=?0.50; P?=?0.007). These correlations were not observed with subcutaneous fat ATX. These results reveal that obesity-associated upregulation of human adipose tissue ATX is specific to the visceral fat depot.     

Dietary monounsaturated fat in early life regulates IGFBP2: implications for fat mass accretion and insulin sensitivity

The aim of this study was to investigate effects of dietary supplementation with fat or sugar on body composition (BC) and insulin sensitivity (IS) in maturing pigs. Fifty newborn pigs randomized to a control diet or 18% saturated fat (SF), 18% monounsaturated fat (MUF), 18% mixed fat (MF), or 50% sucrose (SUC), from 1 to 16 weeks of age. Outcomes included weight gain, BC (dual energy X-ray absorptiometry, DXA), IS (fasting insulin and hyperinsulinaemic-euglycaemic clamps), fasting Non-Esterified Fatty Acid (NEFA) concentrations, and mRNA expression of genes involved in lipogenesis and IS in skeletal muscle (SM), subcutaneous (SAT), and visceral adipose tissue (VAT). In vitro studies examined direct effects of fatty acids on insulin-like growth factor-binding protein 2 (IGFBP2) mRNA in C2C12 myotubes. While SUC-fed pigs gained most weight (due to larger quantities consumed; P < 0.01), those fed fat-enriched diets exhibited more weight gain per unit energy intake (P < 0.001). Total (P = 0.03) and visceral (P = 0.04) adiposity were greatest in MUF-fed pigs. Whole-body IS was decreased in those fed fat (P = 0.04), with fasting insulin increased in MUF-fed pigs (P = 0.03). SM IGFBP2 mRNA was increased in MUF-fed pigs (P = 0.009) and, in all animals, SM IGFBP2 mRNA correlated with total (P = 0.007) and visceral (P = 0.001) fat, fasting insulin (r = 0.321; P = 0.03) and change in NEFA concentrations (r = 0.285; P = 0.047). Furthermore, exposure of in vitro cultured myotubes to MUF, but not SF, reduced IGFBP2 mRNA suggesting a converse direct effect. In conclusion, diets high in fat, but not sugar, promote visceral adiposity and insulin resistance in maturing pigs, with evidence that fatty acids have direct and indirect effects on IGFBP2 mRNA expression in muscle.     

Visceral fat is a determinant of PAI-1 activity in diabetic and non-diabetic overweight and obese women.

Plasminogen activator inhibitor type 1 (PAI-1), an inhibitor of fibrinolysis and an important and independent cardiovascular risk factor, has been shown to be elevated in obesity and type 2 diabetes. Recent study results have suggested that adipose tissue--visceral fat in particular--could play an important role in the fibrinolytic process.In order to assess the specific role of this fat distribution, we measured PAI-1 activity (AU/ml) and visceral fat (CT-scan at level L4-L5) in 2 groups of 30 overweight and obese diabetic and overweight and obese non-diabetic women. Subjects were matched for age, weight, body mass index, fat mass and total abdominal fat. Visceral adipose tissue and PAI-1 were significantly higher in diabetic women (p = 0.022 and p = 0.004 respectively) than in non-diabetic patients. Visceral fat correlated significantly with PAI-1 activity, even after correction for insulin and triglycerides (r = 0.28, p = 0.034). Stepwise regression analysis showed visceral fat as the most important determinant factor for PAI-1 in the whole group and in the non-diabetic group. In the diabetic group, fasting insulin was the most important determinant. These results show that visceral fat is more important than BMI or total body fat in the determination of PAI-1 levels. Furthermore, the increased amount of visceral fat in type 2 diabetics may contribute to the increase of PAI-1 activity levels and the subsequent increased risk for thrombovascular disease, regardless of BMI and total fatness.     

Subcutaneous fat modulates insulin sensitivity in mice by regulating TNF-alpha expression in visceral fat.

The distribution of fat in obese persons is related to the risk of developing various metabolic disorders, such as glucose intolerance, dyslipidemia and hypertension, and the combination of these conditions is known as the metabolic syndrome. The aim of this study was to investigate the role of subcutaneous fat in regulating insulin resistance and its influence on TNF-alpha expression in visceral fat, by using mice that were subjected to subcutaneous lipectomy with or without subsequent fat transplantation. After partial subcutaneous lipectomy, mice showed significantly greater accumulation of visceral fat compared with sham-operated control mice. Lipectomy led to higher plasma insulin and lower plasma glucose levels after loading with glucose and insulin, respectively, compared with the levels in control mice. Insulin-induced phosphorylation of IRS-1 was decreased in the skeletal muscles of lipectomized mice. Subcutaneous transplantation of fat pads into lipectomized mice reversed the above-mentioned changes indicating insulin resistance in these animals. The fat storage area of adipocytes and TNF- alpha expression by adipocytes in visceral fat were significantly higher in the lipectomized mice than in controls, while subcutaneous transplantation of fat reduced both the fat storage area and TNF-alpha expression. The insulin resistance of lipectomized mice was also ameliorated by systemic neutralization of TNF-alpha activity using a specific antibody. These findings obtained in mice subjected to subcutaneous lipectomy with/without subsequent fat transplantation indicate that subcutaneous fat regulates systemic insulin sensitivity, possibly through altering fat storage and the expression of TNF-alpha by adipocytes in visceral fat. The balance between accumulation of subcutaneous fat and visceral fat may be important with respect to the occurrence of systemic insulin resistance in the metabolic syndrome.