Visceral Adipose Tissue Of Rats Research Articles

Fructose consumption enhances glucocorticoid action in rat visceral adipose tissue

The rise in consumption of refined sugars high in fructose appears to be an important factor for the development of obesity and metabolic syndrome. Fructose has been shown to be involved in genesis and progression of the syndrome through deregulation of metabolic pathways in adipose tissue. There is evidence that enhanced glucocorticoid regeneration within adipose tissue, mediated by the enzyme 11beta-hydroxysteroid dehydrogenase Type 1 (11βHSD1), may contribute to adiposity and metabolic disease. 11βHSD1 reductase activity is dependent on NADPH, a cofactor generated by hexose-6-phosphate dehydrogenase (H6PDH). We hypothesized that harmful effects of long-term high fructose consumption could be mediated by alterations in prereceptor glucocorticoid metabolism and glucocorticoid signaling in the adipose tissue of male Wistar rats. We analyzed the effects of 9-week drinking of 10% fructose solution on dyslipidemia, adipose tissue histology and both plasma and tissue corticosterone level. Prereceptor metabolism of glucocorticoids was characterized by determining 11βHSD1 and H6PDH mRNA and protein levels. Glucocorticoid signaling was examined at the level of glucocorticoid receptor (GR) expression and compartmental redistribution, as well as at the level of expression of its target genes (GR, phosphoenolpyruvate carboxyl kinase and hormone-sensitive lipase). Fructose diet led to increased 11βHSD1 and H6PDH expression and elevated corticosterone level within the adipose tissue, which was paralleled with enhanced GR nuclear accumulation. Although the animals did not develop obesity, nonesterified fatty acid and plasma triglyceride levels were elevated, indicating that fructose, through enhanced prereceptor metabolism of glucocorticoids, could set the environment for possible later onset of obesity.

Caloric Restriction Prevents Visceral Adipose Tissue Accumulation and Maintains Erectile Function in Aging Rats

Increased adiposity is an important risk factor for erectile dysfunction (ED) and cardiovascular disease (CVD). Although accumulation of visceral adipose tissue (VAT) is recognized as a key mediator in the pathogenesis of CVD, its role in ED has not been elucidated. To determine whether caloric restriction (CR) could prevent VAT accumulation and thereby prevent the onset of ED in normotensive rats. Male Sprague Dawley rats (10 weeks) were randomized into three dietary groups: ad libitum control (CON), mild CR (CR(MI)), and moderate CR (CR(MOD)). Body weight (BW), body length abdominal girth (AG), and VAT (g-magnetic resonance imaging based) were assessed longitudinally. Erections were assessed using the apomorphine bioassay (80 µg/kg, SQ) after 20 weeks of CR. Excised VAT (mesenteric, epididymal, omental, and retroperitoneal), the internal pudendal artery (IPA) and serum were collected postmortem. Structure and function of the IPA was assessed at study end. Erectile responses, adiposity (VAT), abdominal girth, serum analysis. BW (CON = 653 ± 58.6 g; CR(MI) = 535 ± 47.4 g; CR(MOD) = 409 ± 17.4 g) and VAT (CON = 39 ± 9.0 g; CR(MI) = 30 ± 9.9 g; CR(MOD) = 14 ± 3.5 g) were markedly different between the three groups. AG significantly correlated with longitudinal changes in VAT (R(2) = 0.61) and excised VAT (R(2) = 0.87). CR preserved erectile responses (CON = 0.6 ± 0.45, CR(MI) = 1.2 ± 0.77 g, CR(MOD) = 2.5 ± 0.43 g). A strong inverse correlation between VAT (%) and erectile function was found (R(2) = 0.74) whereas BW was less predictive of ED (R(2) = 0.48). There were no changes in traditional biomarkers (glucose, lipids) which could account for the ED. IPA structure was not different between groups, while CR(MOD) preserved endothelial function. CR effectively prevented VAT accumulation in normotensive rats. Independently of changes in other metabolic markers, this intervention ameliorated the negative impact on erectile responses that occurs with age. Functional changes of the IPA may be a key mechanism by which erections are preserved with CR. AG was shown to be a strong index of VAT in rats.

Chronic ethanol consumption increases the levels of chemerin in the serum and adipose tissue of humans and rats

Chemerin is a new adipokine involved in adipogenesis and insulin resistance. Since ethanol affects the insulin sensitivity that is closely associated with adipokines. The aim of this study was to investigate the effects of ethanol on chemerin in humans and rats. In the human study, 148 men who consumed alcohol for more than 3 years and 55 men who abstained from alcohol were included. Based on ethanol consumption per day, the drinkers were classified into 3 groups: low-dose (<15 g/d), middle-dose (15-47.9 g/d) and high-dose (≥48 g/d). Anthropometric measurements and serum parameters were collected. In the rat study, 27 male Wistar rats were randomly divided into 4 groups administered water or ethanol (0.5, 2.5, or 5 g·kg(-1)·d(-1)) for 22 weeks. The chemerin levels in the sera, visceral adipose tissue (VAT) and liver were measured using ELISA. In the high-dose group of humans and middle- and high-dose groups of rats, chronic ethanol consumption significantly increased the serum chemerin level. Both the middle- and high-dose ethanol significantly increased the chemerin level in the VAT of rats. In humans, triglyceride, fasting glucose, insulin and HOMA-IR were independently associated with chemerin. In rats, the serum chemerin level was positively correlated with chemerin in the VAT after adjustments for the liver chemerin (r=+0.768). High-dose ethanol significantly increased the body fat in humans and the VAT in rats. Chronic ethanol consumption dose-dependently increases the chemerin levels in the serum and VAT. The serum chemerin level is associated with metabolic parameters in humans. The increased serum chemerin level is mainly attributed to an elevation of chemerin in the VAT after the ethanol treatment.

Influence of Quercetin‐rich Onion Peel Extracts on Adipokine Expression in the Visceral Adipose Tissue of Rats

We examined the effects of quercetin-rich onion peel extract supplementation on adipokine expressions from adipose tissues in a diet-induced obese animal model. Male Sprague-Dawley rats (n = 24) were randomly assigned into control (n = 8), high fat diet (HF, n = 8) and high fat diet with onion peel extract (HFOE, n = 8). After 8 weeks, serum biochemical parameters, weights of adipose tissues (epididymal, perirenal and mesenteric fats) and adipokine mRNA levels (adiponectin, IL (interleukin)-6 and visfatin) along with PPAR (peroxisome proliferator-activated receptor) γ2 from adipose tissues were measured. After the 8 week supplementation, mesenteric fat weights were lower in the HFOE group than the HF group (p < 0.05). Adiponectin mRNA levels (mesenteric fats) were remarkably higher in the HFOE group than the other groups (p < 0.05 for both). Levels of PPARγ2 mRNA (mesenteric fats) were significantly higher in the HF group (p < 0.05) than those in the control group, but those in the HFOE group were not different from those in the control group. The IL-6 mRNA levels (perirenal and mesenteric fats) were higher in the HF and HFOE groups, but those in the HFOE group were slightly lower than those in the HF group. In conclusion, quercetin-rich onion peel extract supplementation influenced adipokine expressions, particularly from mesenteric fat, addressing the modulatory effect of this substance on obesity-induced inflammation.

Expression and nutritional regulation of the (pro)renin receptor in rat visceral adipose tissue.

Early life nutritional environment plays an important role in the development of visceral adipose tissue and interacts with nutritional regulations in adulthood, leading to metabolic dysregulations. We hypothesized that the renin-angiotensin system may play a role in the programming-induced development of visceral adipose tissue. We studied, using a model of programming of overweight and glucose intolerance, obtained by post-natal overfeeding with consecutive highfat diet, the status of plasma renin activity and mesenteric adipose renin-angiotensin system, including the recently identified (pro)renin receptor, in adult rats. Post-natal overfeeding or high-fat feeding lead to overweight with increased visceral fat mass and adipocytes surface. When both paradigms were associated, adipocytes surface showed a disproportionate increase. A strong immunoreactivity for (pro)renin receptor was found in stromal cells. Plasma renin activity increased in programmed animals whereas (pro)renin receptor expressing cells density was stimulated by high-fat diet. There was a positive, linear relationship between plasma renin activity and (pro)renin receptor expressing cells density and adipocytes surface. Our experiments demonstrate that association of post-natal overfeeding and high-fat diet increased plasma renin activity and adipose (pro)renin receptor expression. Such phenomenon could explain, at least in part, the associated disproportionate adipocyte hypertrophy and its accompanying increased glucose intolerance.

Effect of exercise performed at anaerobic threshold on serum growth hormone and body fat distribution in obese patients with type 2 diabetes

The mechanism by which exercise reduces visceral fat is not fully understood. We have reported that increase in serum growth hormone (GH) level by mild exercise is associated with increase in lipolysis in type 2 diabetes (T2D), and that GH stimulates lipolysis in rat visceral adipose tissue. The aim of this study was to investigate the effect of GH secretion in response to exercise on visceral fat in obese subjects with T2D. Subjects were divided into exercise (n = 11) and non-exercise (n = 8) groups. Exercise was performed at anaerobic threshold (AT). Blood samples were obtained at weeks 0 and 4. To evaluate the secretion of GH and catecholamines in response to exercise, serum GH and catecholamines levels were measured before and after a bout of exercise on day 1. Visceral fat area (VFA) reduction tended to be greater in exercise group compared to non-exercise group (p = 0.067), whereas subcutaneous fat area (SFA) reduction was not different between two groups. In exercise group, serum GH level tended to increase during exercise, while catecholamines showed no significant changes. The change in serum GH level correlated negatively with the change in VFA during this study, but did not correlate with SFA. The increase in serum insulin-like growth factor-I level in exercise group was 10-fold higher than that in non-exercise group. These results suggest that in obese patients with T2D, exercise performed at AT may reduce visceral fat and the reduction appears to be associated with GH secretion but not with catecholamine in response to exercise.:

Effects of Ovariectomy and Estrogen Replacement Therapy on Visceral Adipose Tissue and Serum Adiponectin Levels in Rats

Excess visceral adipose tissue accumulation after menopause is closely associated with decreased insulin sensitivity and adiponectin levels. The purpose of this study was to determine the effect of ovariectomy and estrogen replacement on visceral fat and serum adiponectin levels in ovariectomized (OVX) rats. Forty 11-week-old female Wistar rats were divided into the four following groups (n = 10 rats per group): sham-operated control (SHAM); sedentary OVX (OVX-SED); OVX with estrogen replacement (OVX-ER); and OVX with sesame oil treatment (OVX-C). Rats in OVX-ER and OVX-C groups received 17β-estradiol valerate (30 µg/kg, subcutaneously) and sesame oil as vehicle, five days a week, respectively. All animals were sacrificed after eight weeks of intervention. Ovariectomy after eight weeks increased body weight and visceral fat (P < 0.05) in OVX-SED and OVX-C groups compared with SHAM rats with no change in plasma adiponectin levels. Estrogen replacement in OVX animals decreased body weight (13.4%, P < 0.05) and visceral fat (10.4%). Although they were not statistically significant, adiponectin, insulin sensitivity and lipid profile of OVX rats were ameliorated with estrogen treatment. We conclude that ovarian hormone withdrawal leads to higher body weight and visceral adipose tissue in rats, but surprisingly does not change adiponectin levels. Although a substantial decrease in body weight was achieved by estrogen replacement therapy in OVX animals, the beneficial metabolic effects of weight loss seems to be only mechanical, having a tendency to improve insulin sensitivity without elevating adiponectin production.

Visceral fat mass determination in rodent: validation of dual-energy x-ray absorptiometry and anthropometric techniques in fat and lean rats

BackgroundBecause abdominal obesity is predisposed to various metabolic disorders, it is of major importance to assess and track the changes with time of this specific fat mass. The main issue for clinicians or researchers is to use techniques for assessing abdominal fat deposition and its accumulation or changes over time, without sacrificing of experimental subjects. In the rat, techniques to investigate in-vivo visceral fat mass are lacking. The purpose of the study was to validate indirect Dual-energy X-ray Absorptiometry technique and abdominal circumference measurement as tools to predict visceral adipose tissue in rats.Forty-three Wistar male rats from different body weight, fat mass and ages were included in the study. Visceral fat mass was assessed by weighing the total perirenal and peri-epididymal adipose tissues after dissection. Statistical methods were used to discriminate the best region of interest allowing the in-vivo measure of Central Fat Mass by DXA. Abdominal circumference was measured at the same time as the DXA scan.ResultsA region of interest including Central Fat Mass from the whole body DXA scan (extending from L2 to L5 vertebrae), correlated strongly with ex-vivo Fat Mass (r = 0.94, p < 0.001). Abdominal circumference correlated significantly with ex-vivo Fat Mass (r = 0.82, p < 0.001) and Central Fat Mass (0.90, p < 0.001) in the whole group of rats. When dividing the whole group into lean and fat rats, correlations remained significant between Central Fat Mass and ex-vivo Fat Mass but disappeared for the lean group between abdominal circumference and ex-vivo Fat Mass.ConclusionsThis study validates the Central Fat Mass determined by DXA as a non-sacrificial technique to assess visceral fat for in-vivo investigations in rats. The abdominal circumference measure appears useful in studying overweight or obese rats. These two techniques could be convenient tools in follow-up and longitudinal studies.

High‐fat Diet Alters PP2A, TC10, and CIP4 Expression in Visceral Adipose Tissue of Rats

The aim of this study was to investigate a possible link between high-fat diet (HFD)-induced obesity and the expression of protein phosphatase 2A (PP2A) and Cdc42-interacting protein 4 (CIP4) proteins, potential downstream components of the IRS/PI3K/AKT and CAP/Cbl/TC10 pathway, respectively, in the visceral adipose tissue. Twenty male Sprague-Dawley rats were randomly divided into two groups and were given either HFD or the normal diet (ND) for 8 weeks. The HFD-induced changes in the expression of the epididymal adipose tissue genes involved in the insulin-signaling pathways were evaluated using real-time reverse-transcription PCR and western blot analysis. The exposure of rats to HFD for 8 weeks resulted in a significant increase in the expression of PP2A at both the transcriptional and translational levels, along with a marked reduction in the levels of phosphorylated AKT and insulin receptor substrate-1 (IRS-1) in the cytosol of visceral adipocytes, compared with the ND rats. Besides, there were significant HFD-induced decreases in the mRNA and protein levels of CIP4 and TC10 in the adipose tissue of rats. These data suggest that HFD might have a relevance to insulin resistance by increasing the expression of PP2A, an inhibitor of AKT activity in the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, and also by suppressing the expression of TC10 and CIP4, downstream effectors of the Cbl/CAP/TC10 insulin-signaling cascade in the visceral adipose tissue.

Anti-obesity Effects of Juniperus chinensis Extract Are Associated with Increased AMP-Activated Protein Kinase Expression and Phosphorylation in the Visceral Adipose Tissue of Rats

This study evaluates the protective effect of Juniperus chinensis hot water extract (JCE) against high-fat-diet (HFD)-induced obesity and its molecular mechanisms in the visceral adipose tissue of rats. JCE supplementation significantly lowered body weight gain, visceral fat-pad weights, blood lipid levels, and blood insulin and leptin levels of rats rendered obese by an HFD. Feeding with JCE significantly reversed the HFD-induced down-regulation of the epididymal adipose tissue genes implicated in adipogenesis, such as the peroxisome proliferator-activated receptors gamma2 (PPARgamma2), adipocyte protein 2 (aP2), sterol regulatory element binding protein 1c (SREBP1c), fatty acid synthase (FAS), and HMG-CoA reductase (HMGR), as well as those involved in uncoupled respiration, such as the uncoupling protein 2 (UCP2) and uncoupling protein 3 (UCP3). Dietary supplementation with JCE also reversed the HFD-induced decreases in the AMP-activated protein kinase (AMPK) and the acetyl-CoA carboxylase 2 (ACC2) expressions at both the mRNA and protein levels and restored the HFD-induced inhibitions in the AMPK and ACC2 phosphorylation, which are related to fatty acid beta-oxidation, in the epididymal adipose tissue. This study reports, for the first time, that the JCE can have an anti-obesity effect in a rodent model with HFD-induced obesity through an enhanced gene transcription of the uncoupling protein as well as an elevated AMPK protein expression and phosphorylation in the visceral adipose tissue.

Effects of dietary carbohydrate on expressions of lipogenic enzymes, insulin receptors and Glut4 in visceral adipose tissue of rats

Effects of dietary carbohydrate on expressions of lipogenic enzymes, insulin receptors and Glut4 in visceral adipose tissue of rats

Effect of PPAR-δ agonist on the expression of visfatin, adiponectin, and resistin in rat adipose tissue and 3T3-L1 adipocytes

It has been recently reported that activation of PPAR-δ, by specific agonists or genetic manipulation, alleviates dyslipidemia, hyperglycemia, and insulin resistance in animal models of obesity and type 2 diabetes. The purpose of the present study was to determine whether the PPAR-δ agonist has a direct effect on adipokines in visceral adipose tissue of rats and in cultured adipocytes. We examined the expression of visfatin, adiponectin, and resistin mRNA in visceral adipose tissue of Wistar rats fed a high-fat diet and 3T3-L1 adipocytes treated with PPAR-δ agonist (L-165041). Body weight and biochemical measurements were performed.Rats fed a high-fat diet showed a greater increase in body weight than those fed a standard diet (P<0.05), and treatment with L-165041 (10mg/kg/day) significantly decreased weight gain (P<0.05). The concentration of total cholesterol was lower, and HDL cholesterol was higher in L-165041-treated rats (P<0.05). In the visceral adipose tissue of L-165041-treated rats, visfatin and adiponectin mRNA levels significantly increased compared to those of the untreated rats (P<0.05). However, the expression of resistin decreased in the L-165041-treated rats. Furthermore, in cultured 3T3-L1 adipocytes, the level of visfatin and adiponectin mRNA was up-regulated in response to L-165041 treatment for nine days. By contrast, resistin mRNA levels were down-regulated by L-165041 treatment. The present study provides a novel evidence to suggest that the PPAR-δ agonist has regulatory effects on a variety of adipokines, and these effects might explain some of their metabolic function.

In vivo and in vitro microdialysis sampling of free fatty acids

Microdialysis is a technique that allows continuous sampling of compounds from the interstitial fluid of different tissues with minimal influence on surrounding tissues and/or whole body function. In the present study, the feasibility of using microdialysis as a technique to sample free fatty acids (FFA) was investigated both in vitro and in vivo, by use of a high molecular weight (MW) cut-off membrane (3 MDa) and a push–pull system to avoid loss of perfusion fluid through the dialysis membrane. The relative recovery was examined in vitro for three different concentrations of radiolabelled oleic acid-BSA solutions (oleic acid:BSA molar ratio 1:1) and for various temperatures and flow rates. The recovery of oleic acid was found to be dependent on the concentration of analyte in the medium surrounding the membrane (17.3%, 29.0% and 30.6% for 50, 100 and 200 μM oleic acid-BSA solutions, respectively). Addition of 0.25% BSA to the perfusion fluid resulted, however, in a concentration-independent recovery of 31.4%, 28.1% and 28.1% for the 50, 100 and 200 μM solutions, respectively. The capability of the method to measure FFA together with glycerol was investigated in vivo in visceral adipose tissue of rats, before and after lipolytic treatment with the β 3-adrenergic agent, BRL37344. BRL37344 caused an increase in both dialysate FFA and glycerol, although the increase was markedly higher for glycerol, amounting to 24.5% and 329.2% increase from baseline, respectively. Subsequent in vitro test of probe performance revealed a decrease in the dialysing properties with regard to FFA, but not glycerol. This suggests that clogging of the membrane pores after 110 min prevented the measurement of the full FFA response in vivo.

Long-term exercise stimulates adenosine monophosphate–activated protein kinase activity and subunit expression in rat visceral adipose tissue and liver

Adenosine monophosphate–activated protein kinase (AMPK) is activated in response to adenosine triphosphate depletion caused by the metabolic and nutritional state. Mammalian AMPK is a heterotrimeric enzyme composed of a catalytic α subunit and 2 regulatory subunits ( β and γ). Although much attention has been focused on exercise-induced AMPK activation in skeletal muscle, little information is available on the role of AMPK in adipose tissue and liver. Acetyl-coenzyme A carboxylase (ACC) is a well-known downstream target of AMPK. The ACC contains serine residues that are phosphorylated by AMPK. The present study was undertaken to determine whether long-term exercise of medium intensity (60% of V˙ o 2max for 12 weeks) may influence AMPK enzyme activity, gene/protein expression, and subsequent ACC phosphorylation in rat adipose tissue (visceral and subcutaneous) and liver. We initially demonstrated that long-term exercise induced a significant increase in phosphorylation of Thr 172 in the AMPK α 1 subunit and of Ser 79 in ACC in visceral adipose tissue rather than subcutaneous tissue. We also demonstrated that the AMPK α 1-, α 2-subunit messenger RNA (mRNA) level as well as the corresponding protein levels were increased in response to long-term exercise, whereas the other subunits were not altered significantly. In contrast to that of visceral adipose tissue, long-term exercise did not induce any significant effect on any of the AMPK subunit mRNA levels or α 1-, α 2-subunit protein levels in subcutaneous adipose tissue. In addition to adipose tissue, we demonstrated that long-term exercise induced an increase in both AMPK/ACC phosphorylation and α 1-, α 2-subunit mRNA/protein expression in the liver. Although the precise physiologic relevance of AMPK activation in these tissues remains unknown, it is possible that it might play an important role in long-term exercise-induced adaptation mechanisms and may lead to an improvement in certain metabolic abnormalities in metabolic diseases.

Perilla Oil Prevents the Excessive Growth of Visceral Adipose Tissue in Rats by Down-Regulating Adipocyte Differentiation ,

We examined the effect of dietary oils with different fatty acid compositions on the growth of visceral adipose tissue in rats. Rats were fed for 4 mo starting at weaning a basal diet containing (12 g/100 g diet) perilla oil rich in (n-3) polyunsaturated fatty acids (PUFA), safflower oil rich in (n-6) PUFA, olive oil rich in monounsaturated fatty acid, or beef tallow rich in saturated fatty acids. The amount of food consumed and body weight gain did not differ among the four dietary groups. The weight of the epididymal fat pad and the serum triglyceride concentration in perilla oil–fed rats were significantly lower (P < 0.05) than those of olive oil– and beef tallow-fed groups. The product of [(volume of individual adipocytes) × (number of adipocytes in epididymal fat pad)], which presumably represents total adipocyte volume in the fat pad, was significantly lower (P < 0.05) in perilla oil–fed rats than in beef tallow– and olive oil–fed groups. Expression of the late genes of adipocyte differentiation, peroxisome proliferator-activated receptor α, adipocyte P2 and adipsin, was significantly (P < 0.05) down-regulated in epididymal fat tissue of rats that had been fed perilla oil rather than beef tallow or olive oil, whereas expression of the early gene, lipoprotein lipase, was not significantly affected. Greater levels (P < 0.05) of (n-3) PUFA in the membrane phospholipid fraction of the fat tissue were observed in perilla oil–fed rats than in the other dietary groups. These results suggest that perilla oil or (n-3) PUFA prevents excessive growth of adipose tissue in rats at least in part by suppressing the late phase of adipocyte differentiation.