Rat Adipose Tissue Research Articles

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.

LCHP Diet Enriched with Cholesterol Promotes Non-Alcoholic Fatty Liver Disease in Wistar Rats

The aim of this study was to analyze the effect of a low-carbohydrate–high-protein diet, enriched with cholesterol (LCHPch), on body weight, lipid metabolism, as well as kidney and liver function in rats. Wistar rats (N = 18, male) were randomly allocated into experimental groups and fed a modified AIN-93G diet with the addition of 1% cholesterol (AINch, WDch and LCHPch diets) for 8 weeks. Despite the lack of significant differences in the final body weight and liver weight of animals, the kidneys of rats in the LCHPch group were considerably heavier compared to the control group. Serum total cholesterol and the sum of low- and very-low-density fractions of cholesterol as well as ALT activity were significantly increased in the LCHPch rats in comparison to the AINch group. Simultaneously, the highest content of liver fat was obtained for animals from LCHPch group. It was also shown that both WDch and LCHPch diets significantly changed fatty acid profile in the adipose tissue of rats compared to control, with a significant increase in SFA and MUFA and a decrease in PUFA. Non-alcoholic fatty liver disease was observed in rats fed not only WDch but also LCHPch diets. The detailed mechanism still needs to be investigated to prevent the organism from the harmful effects of macronutrient dietary imbalance.

The Effect of Swimming Training with Cinnamon Consumption on β3-AR and ERK2 Gene Expression in the Visceral Adipose Tissue of Diabetic Rats

Background: β3-AR is an important factor involved in the activation of ERK protein signaling cascade, which can positively contribute to the regulation of adipose tissue metabolism and its conversion into brown adipose tissue. Diabetes mellitus can lead to dysfunction of these factors. Objectives: The current study aimed to investigate the effect of swimming training combined with cinnamon consumption on β3-AR and ERK2 gene expression in the visceral adipose tissue from diabetic rats. Methods: In this experimental-fundamental study, 35 male Wistar rats (mean weight: 200 ± 20 g) were selected and randomly assigned into four groups after the induction of diabetes by streptozotocin. These groups included: (1) healthy control, (2) control, (3) swimming, (4) cinnamon, and (5) swimming cinnamon (n = 7 in each group). The training groups were put through a five-days-a-week workout for four weeks according to the training protocol. Gene expression levels were measured by in vitro real-time PCR. The collected data were analyzed using one-way ANOVA and Tukey’s post hoc test. Results: The expression levels of β3-AR and ERK2 protein genes in the visceral adipose tissue of diabetic rats (P = 0.0001) were significantly affected by swimming training and cinnamon consumption. Conclusions: It was shown that cinnamon supplementation may have increased β3-AR levels, which was more effective than training, while training had a greater effect on ERK2 levels and increased them. Therefore, it was concluded that cinnamon consumption combined with training may have greatly contributed to the conversion of white adipose into brown adipose tissues.

Effects of Dapagliflozin on Adipose and Liver Fatty Acid Composition and mRNA Expression Involved in Lipid Metabolism in High-Fat-Fed Rats.

SGLT2 inhibitor enhances not only glucose excretion but also fatty acid utilization. Those facts suggest that SGLT2 inhibitor affects fat accumulation and lipid storage. In the present study, we evaluated the effects of dapagliflozin on fatty acid composition and gene expression involved in fatty acid metabolism in rat adipose and liver tissues. We administered 1 mg/kg/day dapagliflozin for 7 weeks to male high-fat-fed rats (DAPA group), and then weights and 22 fatty acid contents in the epididymal (EPI), mesenteric (MES), retroperitoneal (RET), and subcutaneous (SUB) adipose tissues, and the liver were compared with the vehicle-administered control group. In the EPI, RET, and SUB in the DAPA group, contents of several fatty acids were lower (P<0.05) than those in the control group, while no significant difference was detected in tissue weight. In the MES, tissue weight and a wide variety of fatty acid contents, including saturated, monounsaturated, and polyunsaturated fatty acids, were lower (P<0.05). As for the liver tissue, no significant difference was observed in fatty acid contents between the groups. mRNA expression of Srebp1c in EPI was significantly higher (P<0.05) in the DAPA group than in the control group, while Scd1 expression in the liver was lower (P<0.01). These results suggest that dapagliflozin might suppress lipid accumulation especially in the MES, and could reduce contents of fatty acids not in the liver but in adipose tissues in high-fat-fed rats. In addition, dapagliflozin could influence mRNA expression involved in lipogenesis in the EPI and liver.

Ameliorating Inflammation in Insulin-resistant Rat Adipose Tissue with Abdominal Massage Regulates SIRT1/NF-κB Signaling

It was the aim of this study to determine whether abdominal massage reverses high-fat diet-induced insulin resistance compared with RSV treatment. A total of sixty male Sprague-Dawley rats were randomly placed in one of four groups:the non-fat diet (NFD), the high-fat diet (HFD), the HFD with abdominal massage (HFD+ AM), and the HFD plus resveratrol (HFD+ RSV). For eight weeks, rats were fed high-fat diets to create insulin resistance, followed by six weeks of either AM or RSV. Molecular mechanisms of adipogenesis and cytokine production in rats with high-fat diets were investigated. The model rat adipose tissue showed significant improvements in obesity, glucose intolerance, and the accumulation of lipid in the body [the total cholesterol level (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)], metabolic effects of glucose [The fasting blood glucose (FBG), Fasting insulin levels (FINS)], inflammatory status [interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α, C-reactive protein (CRP)], and macrophage polarization after AM or RSV treatment. Further, AM increased SIRT1/NF-κB signaling in rat adipose tissue. Accordingly, in rat adipose tissue, our results indicate that AM regulates the secretion of proinflammatory cytokines, blood sugar levels, and related signaling pathways, contributing to improvement of IR, which may serves as a new therapeutic approach for the treatment for IR.

Exosomes facilitate intercellular communication between uterine perivascular adipose tissue and vascular smooth muscle cells in pregnant rats.

Perivascular adipose tissue (PVAT) is distinct from other adipose depots, as it has differential gene and protein profiles and vasoactive functions. We have shown that pregnancy affects the morphology of PVAT surrounding the uterine arteries (utPVAT) differentially than the morphology of nonperivascular reproductive adipose depots (i.e., periovarian adipose tissue, OVAT). Here, we hypothesized that pregnancy modifies the profile (size and molecular mass) of exosome-like extracellular vesicles released by utPVAT (Exo-utPVAT) compared with exosome-like extracellular vesicles released by OVAT (Exo-OVAT) and that primary uterine vascular smooth muscle cells (utVSMCs) can internalize Exo-utPVAT. Our findings indicate that utPVAT from pregnant and nonpregnant rats secrete exosome-like vesicles. Exo-utPVAT from pregnant rats were smaller (i.e., molecular size) and heavier (i.e., molecular mass) than those from nonpregnant rats, whereas pregnancy did not affect the size of Exo-OVAT. Immunocytochemistry and confocal microscopy showed that primary utVSMCs internalized Exo-utPVAT (both tissues from the same pregnant rat) labeled by the lipophilic tracer DiO. Treatment of isolated uterine arteries with Exo-utPVAT did not affect relaxation responses to acetylcholine in pregnant or nonpregnant rats. Collectively, these findings demonstrate a novel type of intercellular communication between Exo-utPVAT and utVSMCs and indicate pregnancy modulates the morphology and cargo of Exo-utPVAT.NEW & NOTEWORTHY Uterine perivascular adipose tissue secretes exosome-like vesicles, which are internalized by their adjacent uterine vascular smooth muscle cells. Consideration of the exosomal communication between adipose tissue and vascular smooth muscle cells in the uterine circulation in mathematical models and experimental designs may help us to improve understanding of mechanisms underlying uterine artery adaptive responses to a healthy pregnancy and during pregnancy complications.

Effect of Chemically Modified Carbon-Coated Iron Nanoparticles on the Structure of Human Atherosclerotic Plaques Ex Vivo and on Adipose Tissue in Chronic Experiment In Vivo.

The high mortality rate caused by atherosclerosis makes it necessary to constantly search for new and better treatments. In previous reports, chemically modified carbon-coated iron nanoparticles (Fe@C NPs) have been demonstrated a high biocompatibility and promising anti-plaque properties. To further investigate these effects, the interaction of these nanoparticles with the adipose tissue of Wistar rats (in vivo) and human atherosclerotic plaques (ex vivo) was studied. For the in vivo study, cobalt–chromium (CoCr) alloy tubes, which are used for coronary stent manufacturing, were prepared with a coating of polylactic acid (PLA) which contained either modified or non-modified Fe@C NPs in a 5% by weight concentration. The tubes were implanted into an area of subcutaneous fat in Wistar rats, where changes in the histological structure and functional properties of the surrounding tissue were observed in the case of coatings modified with Fe@C NPs. For the ex vivo study, freshly explanted human atherosclerotic plaques were treated in the physiological solution with doses of modified Fe@C NPs, with mass equal to 5% or 25% relative to the plaques. This treatment resulted in the release of cholesterol-like compounds from the surface of the plaques into the solution, thus proving a pronounced destructive effect on the plaque structure. Chemically modified Fe@C NPs, when used as an anti-atherosclerosis agent, were able to activate the activity of macrophages, which could lead to the destruction of atherosclerotic plaques structures. These findings could prove the fabrication of next-generation vascular stents with built-in anti-atherosclerotic agents.

The Association of lncRNA and mRNA Changes in Adipose Tissue with Improved Insulin Resistance in Type 2 Obese Diabetes Mellitus Rats after Roux-en-Y Gastric Bypass.

Objective Roux-en-Y gastric bypass (RYGB) has shown good effects in improving obesity and type II diabetes mellitus (T2DM), but the underlying mechanisms remain unclear. This study explored the changes of related lncRNAs, mRNAs, and signaling pathways in white adipose tissue of T2DM rats after RYGB based on RNA-Seq sequencing, with the aim to provide a theoretical basis for RYGB treatment. Methods T2DM rat models were established by continuous feeding with a high-fat diet and injection of streptozotocin (STZ), after which they underwent RYGB or sham surgery. After the surgery, their body weight was measured weekly. Their fasting blood glucose (FBG) and fasting serum insulin (FSI) were also measured. A homeostasis model assessment of insulin resistance (HOMA-IR) was calculated at weeks 0, 8, and 12. Besides, white adipose tissue of T2DM rats was collected for RNA-Seq sequencing and validated by qRT-PCR. A series of bioinformatics analyses, such as differential expression genes (DEGs) screening, was performed. GO and KEGG functional enrichment analysis and protein-protein interaction (PPI) network construction were conducted based on the sequencing data. Results RYGB surgery could significantly inhibit the weight growth rate and decrease the FBG, FSI, and HOMA-IR of T2DM rats. Bioinformatics analysis of RNA sequencing (RNA-Seq) results revealed that 87 DE- lncRNAs (49 upregulated and 38 downregulated) and 1,824 DEGs (896 upregulated and 928 downregulated) were present in between the RYGB group and Sham group. GO and KEGG analysis showed that the target genes of DEGs and differentially expressed lncRNAs (DE-lncRNAs) were mainly associated with amino acid metabolism, fatty acid metabolism, channel activity, and other processes. In addition, the PPI network diagram also displayed that genes such as Fasn, Grin3a, and Nog could be key genes playing a role after RYGB. qRT-PCR showed that the expression level of Grin3a in the RYGB group was significantly increased compared with the Sham group, while the expression of Fasn and Nog was significantly decreased, which was consistent with the sequencing results. Conclusion Using RNA-Seq sequencing, this study revealed the changes of related lncRNAs, mRNAs, and signaling pathways in the white adipose tissue of T2DM rats after RYGB and identified Fasn, Grin3a, and Nog as potential key genes to function after RYGB.

The Effect of High-Intensity Interval Training on the Adiponectin and TNF-α Levels of Serum and Adipose Tissues in Rats Fed with a High-Fat Diet Plus Sucrose Solution

Background: Adipocytokines secreted by adipose tissue are suggested to play a significant role in developing obesity-related complications. On the other hand, regular high-intensity interval training (HIIT) has been shown to reduce the risk of metabolic complications in obese subjects. Objectives: The effect of HIIT was evaluated on serum and adipose tissues (inguinal and retroperitoneal) adiponectin and TNF-α levels in rats fed with a high-fat diet plus sucrose solution (HFDS). Methods: Thirty-two male Wistar rats were randomly divided into HFDS and standard diet (SD) groups. After 12 weeks, each group was divided into a sedentary group and a HIIT group. An HIIT program was performed three times/week for eight weeks. Inguinal and retroperitoneal adipose tissues and serum were collected to assay adiponectin and TNF-α levels. Also, serum glucose and insulin levels, insulin resistance index (HOMA-IR) were measured. Results: HFDS significantly increased weight gain, weight of inguinal (P = 0.001) and retroperitoneal fat depots (P &lt; 0.001), and HOMA-IR (P &lt; 0.001) but reduced serum TNF-α levels (P = 0.011). HIIT was able to decrease weight gain and fat mass (P &lt; 0.05) but did not affect inguinal and retroperitoneal fat depots’ adipokines (adiponectin and TNF-α) levels and HOMA-IR (P &gt; 0.05). Conclusions: HIIT program can have significant reducing effects on weight gain and fat weights, but it does not effect on circulating and fat depots' adiponectin and TNF-α levels in rats fed a HFDS.

The gene knockout of angiotensin II type 1a receptor improves high-fat diet-induced obesity in rat via promoting adipose lipolysis.

AimsThe renin-angiotensin system (RAS) is over-activated and the serum angiotensin II (Ang II) level increased in obese patients, while their correlations were incompletely understood. This study aims to explore the role of Ang II in diet-induced obesity by focusing on adipose lipid anabolism and catabolism.MethodsRat model of AT1aR gene knockout were established to investigate the special role of Ang II on adipose lipid metabolism. Wild-type (WT) and AT1aR gene knockout (AT1aR-/-) SD rats were fed with normal diet or high-fat diet for 12 weeks. Adipose morphology and adipose lipid synthesis and lipolysis were examined.ResultsAT1aR deficiency activated lipolysis-related enzymes and increased the levels of NEFAs and glycerol released from adipose tissue in high-fat diet rats, while did not affect triglycerides synthesis. Besides, AT1aR knockout promoted energy expenditure and fatty acids oxidation in adipose tissue. cAMP levels and PKA phosphorylation in the adipose tissue were significantly increased in AT1aR-/- rats fed with high-fat. Activated PKA could promote adipose lipolysis and thus improved adipose histomorphology and insulin sensitivity in high-fat diet rats.ConclusionsAT1aR deficiency alleviated adipocyte hypertrophy in high-fat diet rats by promoting adipose lipolysis probably via cAMP/PKA pathway, and thereby delayed the onset of obesity and related metabolic diseases.

BAIBA Involves in Hypoxic Training Induced Browning of White Adipose Tissue in Obese Rats

In recent years, obesity has become an important risk factor for human health; how to effectively prevent and reduce the occurrence of obesity is a hot research topic in recent years. Hypoxic training effectively improves abnormalities of lipid metabolism caused by obesity. The current study explored the effects of hypoxic training on BAIBA secretion and white fat browning in inguinal fat in obese rats. Analyses were performed by HPLC/MS/MS—MS/MS, RT-q PCR and western blot methods. The findings showed that 4 weeks of hypoxic training reduced body weight, Lee’s index, and regulated blood lipid profile in obese rats. Hypoxic training up-regulated BAIBA concentration in gastrocnemius muscle and circulation in obese rats. Hypoxic training significantly upregulated expression of PPARα and UCP-1 in inguinal fat of obese rats and increased white fat browning. The findings showed that BAIBA may involve in improveing blood lipid profile and white fat browning by modulating PPARα and UCP-1 expression.

Comparison the Influence of Various Intensities of Aerobic Training on the Expression of RBL-1 and RB1 Genes in the Subcutaneous Adipose Tissue of Male Wistar Rats

زمینه و هدف: از مهم‌ترین روش‌های مقابله با اختلال متابولیک چاقی، انجام فعالیت‌های ورزشی است که هم به‌عنوان پیشگیری و هم درمان مؤثر است. از آنجا که بیان ژن‌های آدیپوژنیکی مانند پروتئین رتینوبلاستوما 1 (RB1) و شبه‌رتینوبلاستوما-1 (RBL-1) در آدیپوژنز مؤثر است، ازاین‌رو هدف این پژوهش بررسی تأثیر شیوه‌های مختلف تمرین هوازی بر بیان ژن‌های RB1 و RBL-1 در بافت چربی زیر جلدی موش‌های صحرایی نر ویستار بود.مواد و روش‌ها: در این پژوهش تجربی، ۳۲ سر موش صحرایی نر ویستار (هشت‌هفته‌ای و با وزن 33 ± 237 گرم) به‌صورت تصادفی به چهار گروه مساوی کنترل، تمرین پرشدت (HIT)، تمرین با شدت متوسط (MIT) و تمرین تناوبی پرشدت (HIIT) تقسیم شدند. شیوة اجرای تمرینات روی نوار گردان شامل هشت هفته بود، به‌طوری‌که تمرین HIT شامل دویدن با سرعت ۲۰ متر بر دقیقه یا با شدت 65 درصد اکسیژن مصرفی بیشینه (VO2max )، با شیب فزایندة تدریجی به مدت 30 دقیقه بود. تمرین MIT شامل دویدن با شدت 65 درصد VO2max به مدت 37 دقیقه بود و تمرین HIIT شامل چهار وهله تناوب شدید با زمان ۴ دقیقه دویدن با شدت ۹۰ تا ۱۰۰ درصد VO2max و چهار وهله تناوب کم شدت با زمان 3 دقیقه با ۵۰ تا ۶۰ درصد VO2max (در مجموع ۲۸ دقیقه) بود. 24 ساعت پس از آخرین جلسة تمرین حیوانات قربانی شده و بافت چربی زیرجلدی آنها برداشته شد و با روش RT-PCR اندازه‌گیری بیان ژن‌ها صورت گرفت. داده‌های به‌دست‌آمده با توجه به عدم توزیع طبیعی با استفاده از آزمون کروسکال والیس و آزمون تعقیبی بنفرونی از طریق نرم‌افزار آماری SPSS نسخة 24 تجزیه‌وتحلیل شد و سطح معناداری 05/0P< در نظر گرفته شد.نتایج: یافته‌های تحقیق حاضر نشان داد که میزان بیان ژن RB1 تنها در گروه تمرین MIT نسبت به گروه کنترل کاهش معناداری یافت (027/0P=). همچنین بیان ژن RBL-1 فقط در گروه تمرین HIT نسبت به گروه کنترل به‌طور معناداری کمتر بود (028/0P=).نتیجه‌گیری: از آنجا که در این پژوهش فقط تمرینات هوازی MIT و HIT با شدت 65 درصد VO2max توانست بیان ژن‌های RB1 و RBL-1 را کاهش دهد، استفاده از این نوع تمرینات در جهت بهبود اختلالات متابولیکی و مهار آدیپوژنز پیشنهاد می‌شود.

Age and sex influence the response in lipid metabolism of dehydrated Wistar rats

Aging is associated a decrease in thirst sensation, which makes old people more susceptible to dehydration. Dehydration produces energy metabolism alterations. Our objective was to determinate the effect of water deprivation (WD) in the lipid metabolism of old male and female rats. Here we show that in the state of WD, aging and sex alters retroperitoneal white adipose tissue (R-WAT) weight of rats, WD old female rats had more lipolysis products than old male rats, a sexual dimorphism in the hormonal response related with metabolism of the adipose tissue of old rats during WD, the expression of P-para mRNA in R-WAT did not present any alteration in animals submitted to WD, the expression of Aqp7 mRNA in R-WAT is altered by WD, age, and sex. Also, WD stimulated an increase in the plasma concentration of oxytocin and the expression of mRNA of the oxytocin receptors in R-WAT.

Fructose-mediated NLRP3 activation induces inflammation and lipogenesis in adipose tissue

Adipose tissue plays a crucial role in energy intake and regulation of metabolic homeostasis. Fructose consumption implicates in development and progression of metabolic dysfunctions. Fructose is a lipogenic sugar known to induce inflammatory response. However, the role of specific inflammatory signal such as nucleotide-binding and oligomerization domain-like receptor, leucine-rich repeat and pyrin domain containing protein 3 (NLRP3) in fructose-induced inflammatory response and its relevance to lipogenesis in adipose tissue are elusive. We assessed NLRP3 activation and its significance in inflammatory response and lipogenesis in epididymal adipose tissue of 60% fructose diet (HFrD)-fed rats. The long-term consumption of HFrD led to impairment of glucose metabolism, development of visceral adiposity, insulin resistance, and elevation of serum triglycerides level, accompanied by activation of NLRP3 in adipose tissue. NLRP3 inflammasome activation in adipose tissue was associated with up-regulated expression of Nlrp3, Asc, and Caspase-1, and raised caspase-1 activity, which resulted in increased expression of IL-1β and IL-18 and secretion of IL-1β. Moreover, lipid accumulation and expression of transcription factors exacerbating accumulation of lipids were augmented in adipose tissue of HFrD-fed rats. Treatment with glyburide, quercetin or allopurinol corrected HFrD-induced dyslipidemia or hyperuricemia, and blocked NLRP3 activation, leading to mitigated inflammatory signaling and lipid accumulation in adipose tissue, improved glucose tolerance and insulin sensitivity in HFrD-fed rats. These data suggest the role of NLRP3 inflammasome to establish linkage among inflammation, lipid accumulation and insulin resistance in adipose tissue, and targeting NLRP3 inflammasome may be a plausible approach for prevention and management for fructose-induced metabolic impairments.

Effect of Gegen Qinlian Decoction on methylation and expression of Scd1gene in adipose tissue of insulin resistant rats and correlations between methylation and physiological and biochemical parameters

This study aimed to explore the effect of Gegen Qinlian Decoction(GQD) on the methylation and mRNA expression level of stearoyl CoA desaturase(SCD) gene in the adipose tissue of rats with insulin resistance(IR) induced by high-fat diet as well as the correlations between methylation and physiological and biochemical indicators. The animals were divided into seven groups, namely, blank control(C) group, IR model group, low-(1.65 g·kg~(-1)), medium-(4.95 g·kg~(-1)), and high(14.85 g·kg~(-1))-dose GQD(GQDL, GQDM, and GQDH) groups, rosiglitazone(RGN, 5 mg·kg~(-1)) group, and simvastatin(SVT, 10 mg·kg~(-1)) group. The rat epididymal adipose tissue was collected for detecting all the cytosine methylation levels in two fragments of Scd1 gene by bisulfite sequencing PCR(BSP). Scd1-1 was located in CG shores and Scd1-2 in CG islands, including the transcriptional start site(TSS). The Scd1 mRNA level was determined by quantitative real-time PCR(q-PCR). Spearman correlation coefficient was used to analyze the correlations between amplified fragment C methylation and physiological and biochemical indicators. The results showed that GQDM remarkably reversed the elevated CG7 methylation in the TSS upstream region of Scd1-2 triggered by high-fat diet. GQDL significantly reversed the lowered total CG methylation in the downstream region of Scd1-2 induced by the high-fat diet. GQD did not significantly improve the decreased Scd1 mRNA expression caused by high-fat diet. Changes in methylation of the total CG, CG5 and CT11 of Scd1-1 in CG shores exhibited significant negative correlations with the serum triglyceride(TG) but positive correlation with the Scd1 mRNA level. The methylation of several C sites in the TSS upstream region of Scd1-2 was positively correlated with physiological and biochemical parameters. The methylation of several CG sites in the TSS downstream region of Scd1-2 was negatively associated with physiological and biochemical parameters. Besides, the methylation of several CH sites in the downstream fragment was positively correlated with physiological and biochemical parameters. All these have demonstrated that GQD may exert the therapeutic effect by regulating the methylation of CG7 in the TSS upstream region and total CG site in the TSS downstream region of Scd1 gene. The methylation of total CG, CG5 and CT11 sites in CG shores of Scd1 gene may be important targets for regulating Scd1 mRNA level and affecting serum TG.

The Effect of 8 Weeks of High Intensity Training vs High Volume Training on TCF4/CHOP10 Gene Complexes of Subcutaneous Fat Tissue in Male Rats

Background and Objectives This study aims to evaluate the effect of different intensities of aerobic training on the expression of transcription factor 4 (TCF4) and C/EBP homologous protein (CHOP10) genes in subcutaneous adipose tissue of male Wistar rats. Subjects and Methods In this experimental study, 32 male Wistar rats with a mean age of 6 weeks and a weight of 237±33 gr were used. Then, they were randomly divided into four groups of 8, including control group, moderate-intensity aerobic training (MIT), high-intensity aerobic training (HIT), and highintensity interval aerobic training (HIIT). The MIT group trained at an intensity of 65% VO2max for 47 minutes. The HIT group running at a speed of 20 meters per minute with an increasing inclination for 40 minutes. The HIIT group trained at an intensity of 90-100% VO2max for 37 minutes. Adipose tissue sample was collected 24 hours after the last training session to evaluate the expression of TCF4 and CHOP10 genes by real-time PCR method. Results There was a significant difference in the expression of CHOP10 gene in the subcutaneous tissue of male Wistar rats in the HIIT group compared to the MIT and control group (P=0.004). However, no significant difference was observed between HIIT and HIT groups (P=1). In addition, there was a significant difference in TCF4 gene expression in the HIIT group compared to the control group (P=0.006). However, no significant difference was observed between HIIT and HIT groups (P=1) Conclusion The expression level of adipogenic genes decreased after HIIT. These findings indicate that this exercise is effective in controlling the expression of genes involved in fat metabolism.

Chloroquine modulates the sulforaphane anti-obesity mechanisms in a high-fat diet model: Role of JAK-2/ STAT-3/ SOCS-3 pathway

The phytochemical sulforaphane (SFN) has been studied for its potential anti-obesity effect, but neither its molecular targets nor its interaction with the antimalarial drug chloroquine (CQ) has been fully delineated. Therefore, high-fat diet (HFD) obese rats were randomly allocated into one of five groups and were left untreated or gavaged orally with SFN (0.5 or 1 mg/kg), CQ (5 mg/kg), or their combination (0.5/5 mg/kg) for six successive weeks to assess their potential interaction and the enrolled mechanisms. SFN effectively reduced the HFD-induced weight gain, blood glucose, and serum leptin levels, and improved lipid profile. On the molecular level, SFN inhibited the lipogenesis-related enzymes, namely sterol regulatory element-binding protein (SREBP)-1c, fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) in both liver and visceral white adipose tissue (vWAT) of HFD obese rats. SFN also turned off the inflammatory pathway conserved Janus kinase/signaling transducers and activators of transcription/suppressor of cytokine signaling (JAK-2/STAT-3/SOCS-3) in these tissues, as well as the inflammatory markers nuclear factor-kappa (NF-κ) B and interleukin (IL)-22 in serum. In contrast, SFN downregulated the gene expression of microRNA (miR-200a), while significantly increasing the autophagic parameters; viz., beclin-1, autophagy-related protein (ATG)-7, and microtubule-associated protein 2 light chain 3 (LC3-II) in both liver and vWAT. On most of the parameters mentioned above, treatment with CQ solely produced a satisfactory effect and intensified the low dose of SFN in the combination regimen. These findings demonstrated the beneficial effects of using CQ as an add-on anti-obesity medicine to SFN.

Effects of topiramate, bupropion and naltrexone isolated or combined on subcutaneous adipose tissue in obese rats.

ABSTRACTObjective:To evaluate the effects of combining topiramate, bupropion and naltrexone in obesity-induced rats on their weight and subcutaneous adipose tissue.Methods:A total of 40 male Wistar rats were induced to obesity for 8 weeks and the animals were divided into 8 groups: Ctr - control, G0 - Sham, G1 - oral saline solution (1.0mL/day), G2 - topiramate (20.0mg/kg) and bupropion (5.0mg/kg), G3 - naltrexone (20.0mg/kg), G4 - topiramate (20.0mg/kg), G5 - bupropion (5.0mg/kg) and G6 - topiramate (20.0mg/kg), bupropion (5.0mg/kg) and naltrexone (20.0mg/kg). During the experiment, all animals were weighed weekly. After 30 days of treatment animals were euthanized and their skin fragments were processed and stained with hematoxylin and eosin for morphological, morphometric and biochemical analyzes.Results:The only group that presented a decrease in the volume of subcutaneous adipose tissue was G3, but this decrease was not significant when compared with the other groups. The G4, the G5 and the G6 presented increased adipose tissue volume. Data showed that until the eighth week all animals increased their weight by approximately 50%. After treatment animals of all groups, except G3, increased their weight from 4% to 9% approximately. The G3 was the only group that lost weight, but this decrease was not significant.Conclusion:The medicines studied were not efficient in reducing weight in obese rats. However, it should be considered that 30-day treatment period is not enough to observe the stronger effects of these drugs.

Cannabidiol (CBD) Dosing: Plasma Pharmacokinetics and Effects on Accumulation in Skeletal Muscle, Liver and Adipose Tissue.

Oral cannabidiol (CBD) consumption is widespread in North America and Europe, as it has analgesic, neuroprotective and antitumor effects. Although oral CBD consumption in humans affords beneficial effects in epileptic and inflammatory states, its pharmacokinetics and subsequent uptake into tissue are largely unknown. This study investigated plasma pharmacokinetics and accumulation of CBD in gastrocnemius muscle, liver and adipose tissue in adult rats following oral gavage. CBD was fed relative to body mass at 0 (control), 30, 115, or 230 mg/Kg/day for 28 days; with 6 males and 6 females per dosing group. Pharmacokinetics were assessed on day 1 and day 28 in the group receiving CBD at 115 mg/Kg/day. The rise in tissue CBD was closely related to specific pharmacokinetic parameters, and adipose tissue levels were ~10 to ~100 fold greater than liver or muscle. Tissue CBD levels were moderately correlated between adipose and muscle, and adipose and liver, but were highly correlated for liver and muscle. CBD feeding resulted in several gender-specific effects, including changes in pharmacokinetics, relationships between pharmacokinetic parameters and tissue CBD and differences in tissue CBD levels. CBD accumulation in mammalian tissues has the potential to influence receptor binding and metabolism; therefore, the present findings may have relevance for developing oral dosing regimens.

The Effect of α-Lipoic Acid on Oxidative Stress in Adipose Tissue of Rats with Obesity-Induced Insulin Resistance

Correlation between type 2 diabetes and other abnormalities such as obesity with redox balance disturbance was analyzed in many reports. Nonetheless, antioxidants impact on parameters accompanying these conditions is still unknown. Currently the role of redox imbalance in the adipose tissue has gained a lot of attention. We investigated the impact of α-lipoic acid (ALA) on plasma glucose and insulin concentrations, oxidative stress and inflammation parameters in the subcutaneous (SAT) and visceral (VAT) adipose tissue of high fat diet-fed (HFD) rats. Male Wistar rats were randomly divided into three groups (n = 6) - control diet (CTRL), HFD and HFD with α-lipoic acid (HFD+ALA). HFD increased body weight, plasma insulin and glucose as well as leads to oxidative stress parameters in the adipose tissue. ALA supplementation reduced body weight and oxidative stress parameters more effectively in the visceral than subcutaneous adipose tissue of insulin resistant rats. Insulin resistance led to increased enzymatic and non-enzymatic antioxidant systems, protein and lipid glycoxidation, nitrosative stress, and selected inflammatory parameters more in VAT than in SAT of insulin resistant rats. Moreover, ALA inhibited HFD consequences mainly in VAT mostly through glutathione (GSH) biosynthesis.