Visceral Adipose Tissue Of Rats Research Articles

Human recombinant relaxin-2 (serelaxin) regulates the proteome, lipidome, lipid metabolism and inflammatory profile of rat visceral adipose tissue

Recombinant human relaxin-2 (serelaxin) has been widely proven as a novel drug with myriad effects at different cardiovascular levels, which support its potential therapeutic efficacy in several cardiovascular diseases (CVD). Considering these effects, together with the influence of relaxin-2 on adipocyte physiology and adipokine secretion, and the connection between visceral adipose tissue (VAT) dysfunction and the development of CVD, we could hypothesize that relaxin-2 may regulate VAT metabolism. Our objective was to evaluate the impact of a 2-week serelaxin treatment on the proteome and lipidome of VAT from Sprague-Dawley rats. We found that serelaxin increased 1 polyunsaturated fatty acid and 6 lysophosphatidylcholines and decreased 4 triglycerides in VAT employing ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) based platforms, and that regulates 47 phosphoproteins using SWATH/MS analysis. Through RT-PCR, we found that serelaxin treatment also caused an effect on VAT lipolysis through an increase in the mRNA expression of hormone-sensitive lipase (HSL) and a decrease in the expression of adipose triglyceride lipase (ATGL), together with a reduction in the VAT expression of the fatty acid transporter cluster of differentiation 36 (Cd36). Serelaxin also caused an anti-inflammatory effect in VAT by the decrease in the mRNA expression of tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), chemerin, and its receptor. In conclusion, our results highlight the regulatory role of serelaxin in the VAT proteome and lipidome, lipolytic function, and inflammatory profile, suggesting the implication of several mechanisms supporting the potential benefit of serelaxin for the prevention of obesity and metabolic disorders.

The effect of near-infrared rays on the decrease in the number of adipocyte cells using the flow cytometry method

Adipose tissue, composed of adipocyte cells, can become problematic due to an increase in cell number (hyperplasia) and size (hypertrophy). To address this concern, interventions are needed to reduce these probabilities. Near Infrared (NIR) is an electromagnetic wave that affects tissues by being absorbed and penetrating them. NIR can induce cell death (necrosis or apoptosis), where cells respond to external factors causing tissue damage. The purpose of this study was to examine the effect of near-infrared rays on the decrease in the number of adipocyte cells using the flow cytometry method. This study, conducted in vitro using adipocyte cell cultures isolated from rat visceral adipose tissue, explores the effects of NIR exposure at various distances (1 cm, 2 cm, and 3 cm) for 20 minutes. Adipocyte cells were stained and examined using Confocal laser scanning microscopy (CLSM), and the percentage of cells was determined by flow cytometry. Statistical analyses were performed using One Way ANOVA and Duncan test. Significant differences (p-value < 0.05) were observed, and the Duncan test revealed variations in the percentage of living cells among control and treatment groups. The data indicated that exposure to high NIR energy with low wavelengths penetrated adipocyte cells, leading to a decrease in the percentage of cells and notable changes in cell morphology. Flow cytometry results demonstrated differences in live cell percentages, with group 2 (exposed at 2 cm for 20 minutes) being more effective, showing lower percentages of live cells. This research suggests that NIR exposure has an impact on adipocyte cell cultures, emphasizing its potential in influencing adipocyte cell behavior.

Antioxidative Effects of Black Currant and Cornelian Cherry Juices in Different Tissues of an Experimental Model of Metabolic Syndrome in Rats.

A Western-style diet, rich in fat and simple sugars, is the main risk factor for a significant number of chronic diseases and disorders, as well as for a progression of metabolic syndrome (MetS). One of the key mechanisms involved in MetS development is increased oxidative stress caused by the accumulation of body fat. Some dietary polyphenols have shown a protective role in preventing oxidative-stress-induced damage. We investigated the difference in the oxidative response of plasma, liver, and visceral adipose tissue in rats fed with a high-fat high-fructose (HFF) diet for ten weeks, and the effectiveness of polyphenol-rich juices (black currant (BC) and cornelian cherry (CC)) in HFF-diet-induced oxidative stress prevention. The most prominent impact of the HFF diet on redox parameters was recorded in the liver, whereas adipose tissue showed the most potent protection mechanisms against oxidative stress. Consumption of both juices decreased advanced oxidation protein product (AOPP) level in plasma, increased paraoxonase1 (PON1) activity in the liver, and significantly decreased total oxidative status (TOS) in adipose tissue. BC exerted stronger antioxidative potential than CC and decreased the superoxide anion radical (O2•-) level in the liver. It also reduced TOS, total antioxidative status (TAS), and malondialdehyde (MDA) concentration in adipose tissue. The multiple linear regression analysis has shown that the best predictors of MetS development, estimated through the increase in visceral adiposity, were superoxide dismutase (SOD), AOPP, TOS, and TAS. The consumption of polyphenol-rich juices may provide a convenient approach for the systemic reduction of oxidative stress parameters.

Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold

Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold

Effects of the Long-Term Consumption of a High-Sucrose Diet on microRNA Expression in Visceral Adipose Tissue of Rats.

Noncoding microRNAs are involved in lipid and carbohydrate metabolism pathways and are powerful regulators of gene expression. The goals of this study were to evaluate the temporal expression profiles of miRNAs in rat adipose tissue and predict mRNA–microRNA interactions. Newly weaned Wistar rats were divided into groups fed a standard diet and high-sucrose diet (HSD). The HSD contains 66.86% carbohydrates (40.45% standard diet, 40.45% condensed milk, and 8.58% crystal sugar), and the HSD was provided for 4, 8 and 15-week periods to investigate the expression levels of miRNAs in visceral adipose tissue using RT–qPCR. Target selection, enriched pathways and networks were analyzed in silico. The factor consumption time significantly was associated to decreases (p < 0.05) in the expression levels of the following miRNAs: 124-5p, 125-5p, 126-5p, 200c-3p, and 212-3p in all experimental groups. The factor diet significantly influenced rno-miR-124-5p, 200c-3p, and 212-3p expression (p < 0.05). A significant reduction (p < 0.05) in rno-miR-27a-3p expression was observed. The biological processes involved key pathways regulating fat deposition. Our findings provide important insights into downregulated miRNA expression patterns in visceral adipose tissue, adiposity level, hyperinsulinemia and increased VLDL-c and triglyceride levels.

Comprehensive lipidomic analysis reveals regulation of glyceride metabolism in rat visceral adipose tissue by high-altitude chronic hypoxia.

Adipose tissue plays a central role in energy substrate homeostasis and is a key regulator of lipid flow throughout these processes. As hypoxia affects lipid metabolism in adipose tissue, we aimed to investigate the effects of high-altitude chronic hypoxia on lipid metabolism in the adipose tissue of rats using a lipidomic analysis approach. Visceral adipose tissues from rats housed in a high-altitude hypoxia environment representing 4,300 m with 14.07% oxygen (hypoxia group) and from rats housed in a low-altitude normoxia environment representing 41 m with 20.95% oxygen (normoxia group) for 8 weeks were analyzed using an ultra-performance liquid chromatography-Orbitrap mass spectrometry system. After 8 weeks, the body weight and visceral adipose tissue weight of the hypoxia group were significantly decreased compared to those of the normoxia group (p < 0.05). The area and diameter of visceral adipose cells in the hypoxia group were significantly smaller than those of visceral adipose cells in the normoxia group (p < 0.05). The results of lipidomic analysis showed a total of 21 lipid classes and 819 lipid species. The total lipid concentration of the hypoxia group was lower than that in the normoxia group (p < 0.05). Concentrations of diacylglycerols and triacylglycerols in the hypoxia group were significantly lower than those in the normoxia group (p < 0.05). Using univariate and multivariate analyses, we identified 74 lipids that were significantly altered between the normoxia and hypoxia groups. These results demonstrate that high-altitude chronic hypoxia changes the metabolism of visceral adipose glycerides, which may potentially modulate other metabolic processes.

The Effects of High-Protein Diet and Resistance Training on Glucose Control and Inflammatory Profile of Visceral Adipose Tissue in Rats.

High-protein diets (HPDs) are widely accepted as a way to stimulate muscle protein synthesis when combined with resistance training (RT). However, the effects of HPDs on adipose tissue plasticity and local inflammation are yet to be determined. This study investigated the impact of HPDs on glucose control, adipocyte size, and epididymal adipose inflammatory biomarkers in resistance-trained rats. Eighteen Wistar rats were randomly assigned to four groups: normal-protein (NPD; 17% protein total dietary intake) and HPD (26.1% protein) without RT and NPD and HPD with RT. Trained groups received RT for 12 weeks with weights secured to their tails. Glucose and insulin tolerance tests, adipocyte size, and an array of cytokines were determined. While HPD without RT induced glucose intolerance, enlarged adipocytes, and increased TNF-α, MCP-1, and IL1-β levels in epididymal adipose tissue (p < 0.05), RT diminished these deleterious effects, with the HPD + RT group displaying improved blood glucose control without inflammatory cytokine increases in epididymal adipose tissue (p < 0.05). Furthermore, RT increased glutathione expression independent of diet (p < 0.05). RT may offer protection against adipocyte hypertrophy, pro-inflammatory states, and glucose intolerance during HPDs. The results highlight the potential protective effects of RT to mitigate the maladaptive effects of HPDs.

Effect of Aerobic Training and Octopamine Supplementation on the Expression of Octopamine Receptors in the Visceral Adipose Tissue of Rats Exposed to Deep Fried Oils

Background: The use of deep fried oils (DFOs) to cook foods is associated with numerous diseases. Although the role of physical activity and some supplements on fat lipolysis has been established, the effect of aerobic training (AT) and octopamine (Oct) on octopamine receptor-dependent lipolysis pathway is not well understood. Objectives: The present study aimed to investigate the effect of AT and Oct supplementation on the expression of Oct receptors in the visceral adipose tissue of DFO-exposed rats. Methods: In this experimental study, 30 male Wistar rats were divided into (1) healthy control (C), (2) DFO, (3) DFO + Oct, (4) DFO + AT, and (5) DFO + Oct + AT groups. Aerobic training was performed for four weeks, five sessions per week at an intensity of 16 - 26 m/min and equivalent to 50% - 65% VO2max, and Otc supplement was interperitoneally injected at 81 µmol/kg five days a week. Results: Aerobic training and Oct supplementation increased tyramin-R and hormone-sensitive lipase (HSL) (P ≤ 0.05), while Oct significantly decreased G protein-coupled receptors (GPCR) (P ≤ 0.05). Also, the interaction of AT and Oct on GPCR reduction was significant (P ≤ 0.05). Conclusions: It seems that AT and Otc alone improve octopamine receptors and lipolysis markers in the visceral adipose tissue of DFO-treated rats, but these two factors have no interactive effects on this pathway.

Tart cherry (Prunus cerasus L.) dietary supplement modulates visceral adipose tissue CB1 mRNA levels along with other adipogenesis-related genes in rat models of diet-induced obesity.

There is increasing evidence for the involvement of dietary bioactive compounds in the cross-talk modulation of endocannabinoid system and some of the key regulators of transcriptional control for adipogenesis. We aimed to characterize the expression of cannabinoid CB1/CB2 receptors and fatty acid amide hydrolase (FAAH) along with selected adipogenesis-related genes (PPARγ, SREBP-1c and PREF-1), adipocyte-secreted factors (leptin and adiponectin), mitochondrial bioenergetic modulators (PGC-1A and UCP-2), and transient receptor potential vanilloid subtype 1 (TRPV1) and 2 (TRPV2) channels in visceral adipose tissue of rats fed with a high-fat diet (HFD) containing either tart cherry seeds alone or tart cherry seeds and juice for 17weeks. The visceral adipose tissue was weighed and checked the expression of different markers by qRT-PCR, Western blot and immunohistochemistry. Tart cherry supplements were able to downregulate the HFD-induced mRNA expression of CB1 receptor, SREBP-1c, PPARγ, leptin, TRPV1 and TRPV2 resulting in potential anti-adipogenic effects. The present study points out that the intake of bioactive constituents of tart cherry may attenuate the effect of adipogenesis by acting directly on the adipose tissue and modulating the interplay between CB1, PPARγ and TRPV channel gene transcription.

Effects of concurrent training on irisin and fibronectin type-III domain containing 5 (FNDC5) expression in visceral adipose tissue in type-2 diabetic rats

Context Evidence suggests that myokines could have clinical implications for metabolic diseases such as type-2 diabetes. Objective We investigated the effects of concurrent training (CT) on irisin and fibronectin type-III domain containing five (FNDC5) expressions in visceral adipose tissue (VAT) in type-2 diabetic rats. Materials and methods Eighteen male Wistar rats (ages four to eight weeks) became diabetic using nicotinamide and streptozotocin and were assigned to either a control (CON) or a CT group using a randomised block design. The CT group exercised on a motor-driven treadmill at 60 to 75 per cent of VO2max (0% grade) for 10–40 min/day (aerobic training) and performed 10 climbs on a 1-meter ladder utilising weighted resistance of 30–100% of body mass (resistance exercise) for 5 days/week over 8 weeks. Forty-eight hours after the last training session, the VAT of rats was removed and washed. FNDC5-relative gene expression and irisin were measured by the reverse transcription polymerase chain reaction (RT-PCR) method and enzyme-linked immunosorbent assay (ELISA) kit. Additionally, insulin resistance and plasma insulin and glucose levels were determined. Results Our findings revealed that CT significantly increased FNDC5-relative gene expression in the VAT of type-2 diabetic rats compared to controls. Furthermore, eight weeks of CT improved insulin resistance and insulin and glucose levels but did not significantly alter irisin levels in type-2 diabetic rats. Discussion and conclusion The results of this study demonstrated that CT increased FNDC5 mRNA and improved insulin resistance, insulin, and glucose levels. Also observed were increased trends (non-significant, p = .051) in irisin levels. Hence, CT may play a role in attenuating metabolic disorders such as obesity and type-2 diabetes.

3,5-Diiodo-L-Thyronine Exerts Metabolically Favorable Effects on Visceral Adipose Tissue of Rats Receiving a High-Fat Diet.

When administered to rats receiving a high-fat diet (HFD), 3,5-diiodo-L-thyronine (3,5-T2) [at a dose of 25 μg/100 g body weight (BW)] is known to increase energy expenditure and to prevent HFD-induced adiposity. Here, we investigated which cellular and molecular processes in visceral white adipose tissue (VAT) contributed to the beneficial effect of 3,5-T2 over time (between 1 day and 4 weeks following administration). 3,5-T2 programmed the adipocyte for lipolysis by rapidly inducing hormone sensitive lipase (HSL) phosphorylation at the protein kinase A-responsive site Ser563, accompanied with glycerol release at the 1-week time-point, contributing to the partial normalization of adipocyte volume with respect to control (N) animals. After two weeks, when the adipocyte volumes of HFD-3,5-T2 rats were completely normalized to those of the controls (N), 3,5-T2 consistently induced HSL phosphorylation at Ser563, indicative of a combined effect of 3,5-T2-induced adipose lipolysis and increasing non-adipose oxidative metabolism. VAT proteome analysis after 4 weeks of treatment revealed that 3,5-T2 significantly altered the proteomic profile of HFD rats and produced a marked pro-angiogenic action. This was associated with a reduced representation of proteins involved in lipid storage or related to response to oxidative stress, and a normalization of the levels of those involved in lipogenesis-associated mitochondrial function. In conclusion, the prevention of VAT mass-gain by 3,5-T2 occurred through different molecular pathways that, together with the previously reported stimulation of resting metabolism and liver fatty acid oxidation, are associated with an anti adipogenic/lipogenic potential and positively impact on tissue health.

Morus alba L. Diminishes visceral adiposity, insulin resistance, behavioral alterations via regulation of gene expression of leptin, resistin and adiponectin in rats fed a high-cholesterol diet

Ethanolic extract of leaves of Morus alba L. (M. alba), known as white mulberry, was orally administered (100 mg/kg b.wt) for 8 weeks to female Wistar rats that were fed a high-cholesterol diet (HCD), to investigate the potential of M. alba leaves in attenuation of obesity, dyslipidemia, insulin resistance, and deficits in mood, cognitive as well as motor activity that are linked to the adipokines secretions of visceral adipose tissue. Results showed that M. alba diminished body weight gain, hypercholesterolemia, hypertriglyceridemia, atherogenic (AI) & coronary artery indices (CRI), and ameliorated glucose level and insulin resistance index in rats on HCD, compared with untreated HCD rats. Moreover, M. alba administration significantly decreased serum leptin and resistin contents as well as their mRNA expression in visceral adipose tissue, but significantly increased serum adiponectin level, and its mRNA expression in visceral adipose tissue in rats fed on HCD, compared to those in untreated HCD group. Regarding behavioral alterations, M. alba attenuated motor deficit, declined memory, depression and anxiety-like behavior, as well in rats on HCD, compared to that noticed in untreated HCD rats. The current data showed that serum leptin and resistin showed a positive correlation with and body weight gain, triglycerides (TG), AI as well as CRI, but showed a negative correlation with exploration, declined memory, depression- and anxiety-like behavior. Conversely, serum adiponectin showed a negative correlation with and body weight gain, TG, AI as well as CRI, but showed a positive correlation with locomotor activity, exploration, declined memory, and depression- and anxiety-like behavior. In conclusion, M. alba leaves supplementation could attenuate adiposity, insulin resistance behavioral deficits via down-regulation of regulation of gene expression of leptin, resistin, but up-regulation of adiponectin gene expression in the visceral adipose tissue of rats fed a high-cholesterol diet.

Involvement of glucocorticoid prereceptor metabolism and signaling in rat visceral adipose tissue lipid metabolism after chronic stress combined with high-fructose diet.

Both fructose overconsumption and increased glucocorticoids secondary to chronic stress may contribute to overall dyslipidemia. In this study we specifically assessed the effects and interactions of dietary fructose and chronic stress on lipid metabolism in the visceral adipose tissue (VAT) of male Wistar rats. We analyzed the effects of 9-week 20% high fructose diet and 4-week chronic unpredictable stress, separately and in combination, on VAT histology, glucocorticoid prereceptor metabolism, glucocorticoid receptor subcellular redistribution and expression of major metabolic genes. Blood triglycerides and fatty acid composition were also measured to assess hepatic Δ9 desaturase activity. The results showed that fructose diet increased blood triglycerides and Δ9 desaturase activity. On the other hand, stress led to corticosterone elevation, glucocorticoid receptor activation and decrease in adipocyte size, while phosphoenolpyruvate carboxykinase, adipose tissue triglyceride lipase, FAT/CD36 and sterol regulatory element binding protein-1c (SREBP-1c) were increased, pointing to VAT lipolysis and glyceroneogenesis. The combination of stress and fructose diet was associated with marked stimulation of fatty acid synthase and acetyl-CoA carboxylase mRNA level and with increased 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase protein levels, suggesting a coordinated increase in hexose monophosphate shunt and de novo lipogenesis. It however did not influence the level of peroxisome proliferator-activated receptor-gamma, SREBP-1c and carbohydrate responsive element-binding protein. In conclusion, our results showed that only combination of dietary fructose and stress increase glucocorticoid prereceptor metabolism and stimulates lipogenic enzyme expression suggesting that interaction between stress and fructose may be instrumental in promoting VAT expansion and dysfunction.

How high-fat diet and high-intensity interval training affect lipid metabolism in the liver and visceral adipose tissue of rats

Lipogenic and lipolytic pathways are tightly regulated by nuclear receptors and binding proteins, such as farnesoid x receptor (FXR) and sterol regulatory element binding protein 1c (SREBP-1c). We designed this research to study the effects of high-intensity interval training (HIIT) and high-fat diet (HFD) on hepatic and adipose FXR and SREBP-1c gene expression beside the plasma levels of lipid profile and insulin. 24 male Wistar rats were randomly divided into normal (~12% fat) and HFD (~56% fat) groups with or without participating in the 8 weeks HIIT protocol. Results from two-way ANOVA and Pearson tests (P&lt;0.05) showed that the HFD rats experienced a larger weight gain correlated with dyslipidemia and hyperinsulinemia, higher hepatic and adipose SREBP-1c expression and lower hepatic FXR expression compared with normal diet fed rats. Although HIIT rats showed higher hepatic FXR and lower hepatic and adipose SREBP-1c expression and lower weight gain compared with untrained rats, plasma lipid profile levels had not any significant difference between trained and untrained rats. Interestingly, hepatic FXR expression was negatively correlated with weight gain and SREBP-1c expression in both tissues while only the hepatic SREBP-1c was positively correlated to insulin levels. In conclusion, HFD-induced dyslipidemia could occur via the activation of the hepatic SREBP-1c pathway under the insulin effect. Although HIIT rats showed lower SREBP-1c correlated to hepatic FXR activation it seems diet is more effective on lipid profile than HIIT. Also, in presence of HFD, HIIT only affects adipose lipolysis.

ANGIOTENSIN II DI PERBENIHAN ADIPOSIT YANG DIPAJAN GLUKOSA TINGGI

Abdominal obesity is closely linked to the occurrence of metabolic syndrome. In pathomechanism of metabolic syndrome, adipocity plays an important role as an active metabolic endocrine organ. This is accomplished the secretion of various hormones, enzymes, cytokines, and components that play a role in the rennin angiotensin system (RAS). One of the mechanisms linking the occurrence of hypertension in obesity is through the increased activity of RAS. Angiotensin II is the major effector of hypertension. The effect of high glucose exposure in adipocytes culture to angiotensin II secretion up to now is yet unknown. Adipociyties culture from rat visceral adipose tissue were exposed to 5 mM glucose concentration (as a physiological condition), 11 mM and 25 mM glucose concentration as the high glucose condition. Measurement of the angiotensin II level which is secreted in the culture medium was done by ELISA method. The mean (SD) levels of angiotensin II were 56.4 (4.28), 66.05 (2.24), and 69.22 (3:49) ng/mL respectively, for adipocities cultures exposed to 5 mM, 11 mM and 25 mM glucose concentration. High glucose exposure could increase the secretion of angiotensin II significantly in adipocytes culture. This suggests that the condition of hyperglycemia affects adipocytes dysfunction that play a role in the metabolic syndrome pathomechanism.

Suppression of isoproterenol-induced lipolysis by insulin in rat visceral adipose tissue explants is increased with aging: Consequences on adiposity

Suppression of isoproterenol-induced lipolysis by insulin in rat visceral adipose tissue explants is increased with aging: Consequences on adiposity

Estrogen deficiency in ovariectomized rats: can resistance training re-establish angiogenesis in visceral adipose tissue?

OBJECTIVE:The purpose of this study was to investigate the effects of resistance training on angiogenesis markers of visceral adipose tissue in ovariectomized rats.METHOD:Adult Sprague-Dawley female rats were divided into four groups (n=6 per group): sham-sedentary, ovariectomized sedentary, sham-resistance training and ovariectomized resistance training. The rats were allowed to climb a 1.1-m vertical ladder with weights attached to their tails and the weights were progressively increased. Sessions were performed three times per week for 10 weeks. Visceral adipose tissue angiogenesis and morphology were analyzed by histology. VEGF-A mRNA and protein levels were analyzed by real-time PCR and ELISA, respectively.RESULTS:Ovariectomy resulted in higher body mass (p=0.0003), adipocyte hypertrophy (p=0.0003), decreased VEGF-A mRNA (p=0.0004) and protein levels (p=0.0009), and decreased micro-vascular density (p=0.0181) in the visceral adipose tissue of the rats. Resistance training for 10 weeks was not able to attenuate the reduced angiogenesis in the visceral adipose tissue of the ovariectomized rats.CONCLUSION:Our findings indicate that the resistance training program used in this study could not ameliorate low angiogenesis in the visceral adipose tissue of ovariectomized rats.

Possible involvement of glucocorticoids in 5α-dihydrotestosterone-induced PCOS-like metabolic disturbances in the rat visceral adipose tissue

Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disorder characterized by hyperandrogenism, ovulatory dysfunction, visceral obesity and insulin resistance. We hypothesized that changes in glucocorticoid metabolism and signaling in the visceral adipose tissue may contribute to disturbances of lipid metabolism in the rat model of PCOS obtained by 5α-dihydrotestosterone (DHT) treatment of prepubertal female Wistar rats. The results confirmed that DHT treatment caused anovulation, obesity and dyslipidemia. Enhanced glucocorticoid prereceptor metabolism, assessed by elevated intracellular corticosterone and increased 11 beta-hydroxysteroid dehydrogenase type 1 mRNA and protein levels, was accompanied by glucocorticoid receptor (GR) nuclear accumulation. In concert with the increased expression of GR-regulated prolipogenic genes (lipin-1, sterol regulatory element binding protein 1, fatty acid synthase, phosphoenolpyruvate carboxykinase), histological analyses revealed hypertrophic adipocytes. The results suggest that glucocorticoids influence lipid metabolism in the visceral adipose tissue in the way that may contribute to pathogenesis of metabolic disturbances associated with PCOS.

Dietary fructose-related adiposity and glucocorticoid receptor function in visceral adipose tissue of female rats

Excessive fructose intake coincides with the growing rate of obesity and metabolic syndrome, with women being more prone to these disorders than men. Findings that detrimental effects of fructose might be mediated by glucocorticoid regeneration in adipose tissue only indirectly implicated glucocorticoid receptor (GR) in the phenomenon. The aim of the present study was to elucidate whether fructose overconsumption induces derangements in GR expression and function that might be associated with fructose-induced adiposity in females. We examined effects of fructose-enriched diet on GR expression and function in visceral adipose tissue of female rats. Additionally, we analyzed the expression of genes involved in glucocorticoid prereceptor metabolism [11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and hexose-6-phosphate dehydrogenase], lipolysis (hormone-sensitive lipase) and lipogenesis (sterol regulatory element binding protein 1 and peroxisomal proliferator-activated receptor γ). Fructose-fed rats had elevated energy intake that resulted in visceral adiposity, as indicated by increased visceral adipose tissue mass and its share in the whole-body weight. GR hormone binding capacity and affinity, as well as the expression of GR gene at both mRNA and protein levels were reduced in visceral adipose tissue of the rats on fructose diet. The glucocorticoid prereceptor metabolism was stimulated, as evidenced by elevated tissue corticosterone, while the key regulators of lipolysis and lipogenesis remained unaffected by fructose diet. The results suggest that the 11βHSD1-mediated elevation of intracellular corticosterone may induce GR downregulation, which may be associated with failure of GR to stimulate lipolysis in fructose-fed female rats.

Dynamic CCAAT/Enhancer Binding Protein–Associated Changes of DNA Methylation in the Angiotensinogen Gene

DNA methylation patterns are maintained in adult somatic cells. Recent findings, however, suggest that all methylation patterns are not preserved. We demonstrate that stimulatory signals can change the DNA methylation status at a CCAAT/enhancer binding protein (CEBP) binding site and a transcription start site and activate expression of the angiotensinogen gene (AGT). A CEBP binding site in the human AGT promoter was hypomethylated in tissues with high expression of AGT, but not in those with low expression. The transcriptional activity of AGT promoter sequences cloned into a reporter plasmid depended on DNA methylation. In cultured human cells, interleukin 6 stimulation caused DNA demethylation around a CEBP binding site and a transcription start site; demethylation was accompanied by increased CEBP-β recruitment and chromatin accessibility of the AGT promoter. DNA methylation activity decreased in the nucleus. Excess circulating aldosterone upregulated AGT expression and was accompanied by DNA hypomethylation around a CEBP binding site and a transcription start site in human visceral adipose tissue. High salt intake led to upregulation of Agt expression, DNA hypomethylation around 2 CEBP binding sites and a transcription start site, and decreased DNA methylation activity in rat visceral adipose tissue. Taken together, CEBP binding initiates chromatin relaxation and transcription, which are followed by DNA demethylation around a CEBP binding site and a transcription start site in the AGT promoter. Decreased DNA methylation activity in the nucleus may play a role in DNA demethylation. DNA demethylation switches the phenotype of AGT expression from an inactive to an active state.