Rat Adipose Tissue Research Articles

Acer tegmentosum Maxim Inhibits Adipogenesis in 3t3-l1 Adipocytes and Attenuates Lipid Accumulation in Obese Rats Fed a High-Fat Diet.

We investigated the effect of Acer tegmentosum Maxim (ATM) on adipocyte differentiation in 3T3-L1 cells and anti-obesity properties in obese rats fed a high-fat diet (HFD). Cellular lipid content in DMI (dexamethasone, 3–isobutyl–1–methylxanthine, and insulin mixture)-treated cells increased, while ATM treatment caused a significant reduction in lipid accumulation in differentiated 3T3-L1 cells. ATM (60 ug/mL) caused inhibition of adipogenesis via down-regulation of the CCAAT/enhancer binding protein β (C/EBPβ) (48%), C/EBPα (66%), and peroxisome proliferator-activated receptor γ (PPARγ) (64%) expressions in 3T3-L1 cells. Moreover, ATM induced a decrease in the expressions of adipocyte-specific genes, such as adipocyte fatty acid-binding protein-2 (aP2), fatty acid synthase (FAS), and lipoprotein lipase (LPL). Protein kinase B (Akt) and glycogen synthase kinase 3β (GSK3β) phosphorylation was also decreased by ATM treatment of 3T3-L1 adipocytes. We investigated the anti-obesity effects of ATM on HFD-induced obese rats. Rats fed with an HFD demonstrated elevations in body weight gain, while the administration of ATM reversed body weight (BW) gains and adipose tissue weights in rats fed an HFD. ATM supplementation caused a decrease in the circulating triglyceride and total cholesterol levels and led to inhibition of lipid accumulation in the adipose tissues in HFD-induced obese rats. Epididymal fat exhibited significantly larger adipocytes in the HFD group than it did in the ATM-treated group. These results demonstrate that ATM administration caused a reduction in adiposity via attenuation in adipose tissue mass and adipocyte size.

Insulin-Regulated Aminopeptidase Inhibition Ameliorates Metabolism in Obese Zucker Rats.

The aim of our study was to determine the influence of inhibition of insulin-regulated aminopeptidase/oxytocinase (IRAP) on glucose tolerance and metabolism of skeletal muscle and visceral adipose tissue in obese Zucker rats. Obese Zucker rats administered with IRAP inhibitor–HFI-419 at a dose of 29 μg/100 g BW/day by osmotic minipumps implanted subcutaneously for 2 weeks. Two-hour intraperitoneal glucose tolerance test (ipGTT) was performed in fasting rats. Plasma oxytocin levels were measured by enzyme immunoassay after plasma extraction. In the musculus quadriceps and epididymal adipose tissue, the expression of factors affecting tissue oxidative status and metabolism was determined by real-time qPCR and/or Western blot analysys. The plasma and tissue enzymatic activities were determined by colorimetric or fluorometric method. Circulated oxytocin levels in obese animals strongly tended to increase after HFI-419 administration. This was accompanied by significantly improved glucose utilization during ipGTT and decreased area under the curve (AUC) for glucose. In skeletal muscle IRAP inhibitor treatment up-regulated enzymes of antioxidant defense system – superoxide dismutase 1 and 2 and improved insulin signal transduction pathway. HFI-419 increased skeletal muscle aminopeptidase A expression and activity and normalized its plasma levels in obese animals. In epididymal adipose tissue, gene expression of markers of inflammation and adipocyte hypertrophy was down-regulated in obese rats after HFI-419 treatment. Our results demonstrate that IRAP inhibition improves whole-body glucose tolerance in insulin-resistant Zucker fatty rats and that this metabolic effect of HFI-419 involves ameliorated redox balance in skeletal muscle.

The effects of weight loss intervention program on serum leptin level, histological and molecular alterations of adipose tissue in rat model with obesity.

Background: Obesity is a resilient and complex chronic disease. Leptin is an adipocyte-derived hormone acts as a key regulator of feeding and energy expenditure. The aim of our study was to assess the level of serum leptin as well as leptin immuno-histochemistry expression in adipose tissue in obese and non-obese rats. Leptin was markedly detected in young preadipocytes during lipogenesis (before weight loss (regime) in contrast to adipocytes undergoing lipolysis (after weight loss (regime) in the later weak positive.

L-carnitine improves metabolic disorders and regulates apelin and apelin receptor genes expression in adipose tissue in diabetic rats.

Apelin is a new adipocytokine that acts as an endogenous hormone in various tissues through its receptor (APJ). This study aimed to investigate the effects of oral administration of L‐carnitine (LC) on the expression of Apelin and APJ in adipose tissue of experimentally induced insulin‐resistant and type 2 diabetic rats. In this experimental study, 60 male rats fed with high fat/high carbohydrate (HF/HC) diet. After 50 mg/kg intraperitoneally injection of streptozotocin (STZ) and confirmation of diabetes (FBS higher than 126 mg/dl), the animals were daily treated with 300 mg/kg LC for 28 days. At days 7, 14, and 28 of posttreatment, the expression of apelin and APJ in adipose tissue were determined using qPCR in diabetic, diabetic + LC treated, control, and control + LC treated groups. Apelin, insulin, TNF‐α, and IL1‐β were measured by the ELISA method. Results demonstrated that the rats fed with the HF/HC diet for 5 weeks were hyperinsulinemic and normoglycemic, while after STZ injection, they showed hyperinsulinemia and hyperglycemia with higher levels of HOMA‐IR. Apelin serum level, APJ and apelin gene expression in adipose tissue increased significantly with the development of diabetes compared to the control group. Treatment with LC for 14 days caused a reduction in apelin and APJ expressions in adipose tissue of diabetic rats. TNF‐α and IL1‐β levels were reduced in diabetic rats 14 days after their treatment with LC. The study results show that L‐carnitine could act as a new regulator in apelin gene expression in adipose tissue, improving the metabolic disorders in diabetic patients.

Diets enriched with coconut, fish, or olive oil modify peripheral metabolic effects of ozone in rats

Dietary factors may modulate metabolic effects of air pollutant exposures. We hypothesized that diets enriched with coconut oil (CO), fish oil (FO), or olive oil (OO) would alter ozone-induced metabolic responses. Male Wistar-Kyoto rats (1-month-old) were fed normal diet (ND), or CO-, FO-, or OO-enriched diets. After eight weeks, animals were exposed to air or 0.8 ppm ozone, 4 h/day for 2 days. Relative to ND, CO- and OO-enriched diet increased body fat, serum triglycerides, cholesterols, and leptin, while all supplements increased liver lipid staining (OO > FO > CO). FO increased n-3, OO increased n-6/n-9, and all supplements increased saturated fatty-acids. Ozone increased total cholesterol, low-density lipoprotein, branched-chain amino acids (BCAA), induced hyperglycemia, glucose intolerance, and changed gene expression involved in energy metabolism in adipose and muscle tissue in rats fed ND. Ozone-induced glucose intolerance was exacerbated by OO-enriched diet. Ozone increased leptin in CO- and FO-enriched groups; however, BCAA increases were blunted by FO and OO. Ozone-induced inhibition of liver cholesterol biosynthesis genes in ND-fed rats was not evident in enriched dietary groups; however, genes involved in energy metabolism and glucose transport were increased in rats fed FO and OO-enriched diet. FO- and OO-enriched diets blunted ozone-induced inhibition of genes involved in adipose tissue glucose uptake and cholesterol synthesis, but exacerbated genes involved in adipose lipolysis. Ozone-induced decreases in muscle energy metabolism genes were similar in all dietary groups. In conclusion, CO-, FO-, and OO-enriched diets modified ozone-induced metabolic changes in a diet-specific manner, which could contribute to altered peripheral energy homeostasis.

Metformin ameliorates olanzapine-induced insulin resistance via suppressing macrophage infiltration and inflammatory responses in rats

AimsThe present study aimed to investigate the possible effects of metformin on the olanzapine-induced insulin resistance in rats. MethodsRats were randomly divided into three groups: the control (Control) group, the olanzapine (Ola) group and the olanzapine + metformin (Ola + Met) group. Rats in the Ola group received olanzapine (8 mg/kg/day) intraperitoneally while rats in the Ola + Met group received olanzapine (8 mg/kg/day) intraperitoneally and metformin (300 mg/kg/day) orally for 8 weeks. Rats in the Control group received vehicle accordingly. Body weight and fasting blood glucose were recorded routinely. Inflammatory cytokines TNF-α, IL-6 and IL-1β and IL-10 were measured by ELISA. The gene expression of macrophages markers was examined by qPCR. The epididymal white adipose tissue, liver and skeletal muscle were also isolated for immunohistochemical analysis. ResultsOlanzapine significantly induced body weight gain and insulin resistance compared to the control, which was markedly alleviated by metformin. Pro-inflammatory cytokines TNF-α, IL-6 and IL-1β were upregulated while the anti-inflammatory cytokine IL-10 was downregulated by olanzapine in plasma and epididymal white adipose tissue compared to the control, but not the liver and skeletal muscle. However, metformin co-administration significantly decreased the levels of TNF-α, IL-6 and IL-1β while increased the level of IL-10 in epididymal white adipose tissue compared to olanzapine-treated rats. Moreover, olanzapine treatment markedly increased the expression of the CD68 and the M1 macrophage markers while decreased the expression of the M2 macrophage markers in epididymal white adipose tissue in rats compared to the control. However, metformin co-treatment ameliorated the effects of olanzapine. ConclusionsOur results suggest that metformin alleviated olanzapine-induced insulin resistance possibly by suppressing the inflammatory responses mediated by macrophage infiltration and polarization in epididymal white adipose tissue.

Effect of high-fat diet and exercise on asprosin and CTRP6 expression in subcutaneous and retroperitoneal adipose tissues in rats during mid-gestation

To study the effects of high-fat (HF) diet and exercise on the expressions of asprosin and CTRP6 in adipose tissues in different regions of rats during mid-gestation. Pregnant SD rats were fed on a standard chow diet or a high-fat (60% fat content) diet for 14 days starting on gestation day (GD) 1. Starting from GD3, the rats fed either on normal or high-fat diet in the exercise groups (CH-RW and HF-RW groups) were allowed access to the running wheels for voluntary running, and those in sedentary groups (CH-SD and HF-SD groups) remained sedentary. At the end of the 14 days, adipose tissues were sampled from different regions of the rats for detecting the mRNA and protein expressions of asprosin and CTRP6 using RT-qPCR and Western blotting. The mRNA expression of asprosin in retroperitoneal adipose tissues was significantly higher in HF-RW group than in the other 3 groups (P < 0.0001). Asprosin mRNA expression in subcutaneous adipose tissues was significantly higher in HF-SD group than in CH-SD group (P=0.0234) and comparable between HF-RW and CH-SD groups (P=0.0494). CTRP6 mRNA expression in retroperitoneal adipose tissues was also significantly higher in HF-RW group than in the other groups (P < 0.0001), and CTRP6 protein expression was signficiantly higher in HF-RW group than in CH-RW and HF-SD groups (P < 0.05). In subcutaneous adipose tissues, CTRP6 mRNA expression was significantly higher in CH-RW group than in HF-SD and HF-RW groups (P < 0.05). The protein expression level of CTRP6 in subcutaneous adipose tissues showed a significant negative correlation with blood glucose (r=-0.6038, P=0.0172), while its expression in retroperitoneal adipose tissues was positively correlated with blood glucose (r=0.5305, P= 0.0285); the mRNA expression levels of asprosin and CTRP6 were significantly lower in subcutaneous than in retroperitoneal adipose tissues (P < 0.0001). High-fat diet and exercise during mid-gedtation can affect the expression levels of asprosin and CTRP6 in adipose tissues of rats in a site-specific manner.

A Mix of Natural Bioactive Compounds Reduces Fat Accumulation and Modulates Gene Expression in the Adipose Tissue of Obese Rats Fed a Cafeteria Diet.

Scientists are focusing on bioactive ingredients to counteract obesity. We evaluated whether a mix containing grape seed proanthocyanidin extract (GSPE), anthocyanins, conjugated linoleic acid (CLA), and chicken feet hydrolysate (CFH) could reduce body fat mass and also determined which mechanisms in the white adipose tissue (WAT) and the brown adipose tissue (BAT) were affected by the treatment. The mix or vehicle (VH) were administered for three weeks to obese rats fed a cafeteria (CAF) diet. Biometric measures, indirect calorimetry, and gene expression in WAT and BAT were analyzed as was the histology of the inguinal WAT (IWAT). The individual compounds were also tested in the 3T3-L1 cell line. The mix treatment resulted in a significant 15% reduction in fat (25.01 ± 0.91 g) compared to VH treatment (21.19 ± 1.59 g), and the calorimetry results indicated a significant increase in energy expenditure and fat oxidation. We observed a significant downregulation of Fasn mRNA and an upregulation of Atgl and Hsl mRNA in adipose depots in the group treated with the mix. The IWAT showed a tendency of reduction in the number of adipocytes, although no differences in the total adipocyte area were found. GSPE and anthocyanins modulated the lipid content and downregulated the gene and protein levels of Fasn compared to the untreated group in 3T3-L1 cells. In conclusion, this mix is a promising treatment against obesity, reducing the WAT of obese rats fed a CAF diet, increasing energy expenditure and fat oxidation, and modifying the expression of genes involved in lipid metabolism of the adipose tissue.

Altered vitamin D3 metabolism in the ovary and periovarian adipose tissue of rats with letrozole-induced PCOS

Vitamin D3 (VD3) plays an important role in the ovary and its deficiency is associated with ovarian pathologies, including polycystic ovary syndrome (PCOS). However, there is no data related to VD3 metabolism in the ovary during PCOS. Herein, we investigated differences in the expression of VD3 receptor (VDR) and key VD3 metabolic enzymes, 1α-hydroxylase (CYP27B1) and 24-hydroxylase (CYP24A1), in the ovary and periovarian adipose tissue (POAT) of control (proestrus and diestrus) and PCOS induced by letrozole rats. Vdr, Cyp27b1 and Cyp24a1 mRNA expression was determined, their protein abundance was examined and immunolocalized. Furthermore, VD3 metabolite concentrations in plasma (25OHD) and tissues (ovary and POAT; 1,25(OH)2D3), and plasma calcium level were determined. 25OHD concentration decreased markedly in letrozole-treated rats in comparison with controls, whereas calcium concentration did not vary among the examined groups. The amount of 1,25(OH)2D3 decreased in both ovary and POAT of PCOS rats. In the ovary, we found decreased Cyp27b1 and increased Vdr mRNA expression in letrozole-treated and diestrus control group. Corresponding protein abundances were down-regulated and up-regulated, respectively but only following letrozole treatment. In POAT, only Cyp27b1 transcript level and CYP27B1 protein abundance were decreased in letrozole-treated rats. VDR was immunolocalized in healthy and cystic follicles, while CYP27B1 and CYP24A1 were found exclusively in healthy ones. Concluding, our results provide the first evidence of disrupted VD3 metabolism in the ovary and POAT of PCOS rats. The reduced 1,25(OH)2D3 concentration in those tissues suggests their contribution to VD3 deficiency observed in PCOS and might implicate in PCOS pathogenesis.

Fasting and refeeding cycles alter subcutaneous white depot growth dynamics and the morphology of brown adipose tissue in female rats.

Intermittent food restriction (IFR) is used mainly for weight loss; however, its effects on adipose tissue are not known when alternating with an obesogenic diet. To demonstrate its effects on morphological dynamics of fat deposits, female Wistar rats were distributed into groups: standard control (ST-C), with commercial diet; DIO control (DIO-C), with a diet that induces obesity (DIO) during the first and last 15 d, replaced by a standard diet for thirty intermediate days; standard restricted (ST-R), with standard diet during the first and last 15 d, with six cycles of IFR at 50 % of ST-C; and DIO restricted (DIO-R), in DIO during the first and last 15 d, with six cycles of IFR at 50 % of DIO-C. At 105 d of life, white adipose tissue (WAT) and brown adipose tissue (BAT) deposits were collected, weighed and histology performed. The DIO-R group showed higher total food intake (DIO-R 10 768·0 (SEM 357·52) kJ/g v. DIO-C 8868·6 (SEM 249·25) kJ/g, P < 0·0001), energy efficiency during RAI (DIO-R 2·26 (SEM 0·05) g/kJ v. DIO-C 0·70 (SEM 0·03) g/kJ, P < 0·0001) and WAT (DIO-R 5·65 (SEM 0·30) g/100 g v. DIO-C 4·56 (SEM 0·30) g/100 g) than their respective control. Furthermore, IFR groups presented hypertrophy of WAT and BAT, as well as fibrosis in BAT. Thus, IFR can establish prospective resistance to weight loss by favouring changes in adipose tissue morphology, increased energy intake and efficiency. Finally, the DIO diet before and after IFR aggravates the damages caused by the restriction.

Engineered Cell Sheets for the Effective Delivery of Adipose-Derived Stem Cells for Tendon-to-Bone Healing

Background: Efforts are being made to treat rotator cuff tears (RCTs) that exhibit poor healing and high retear rates. Tendon-to-bone healing using mesenchymal stem cells is being explored, but research is needed to establish effective delivery options. Purpose: To evaluate the effects of an adipose-derived stem cell (ADSC) sheet on mesenchymal stem cell delivery for tendon-to-bone healing of a chronic RCT in rats and to demonstrate that ADSC sheets enhance tendon-to-bone healing. Study Design: Controlled laboratory study. Methods: Mesenchymal stem cells were obtained from rat adipose tissue, and a cell sheet was prepared using a temperature-responsive dish. To evaluate the efficacy of stem cells produced in a sheet for the lesion, the experiment was conducted with 3 groups: repair group, cell sheet transplantation after repair group, and cell sheet–only group. Histological, biomechanical, and micro–computed tomography (micro-CT) results were compared among the groups. Results: Hematoxylin and eosin staining for histomorphological analysis revealed that the cell sheet transplantation after repair group (5.75 ± 0.95) showed statistically significant higher scores than the repair (2.75 ± 0.50) and cell sheet–only (3.25 ± 0.50) groups (P < .001). On safranin O staining, the cell sheet transplantation after repair group (0.51 ± 0.04 mm2) had a larger fibrocartilage area than the repair (0.31 ± 0.06 mm2) and cell sheet–only (0.32 ± 0.03 mm2) groups (P = .001). On micro-CT, bone volume/total volume values were significantly higher in the cell sheet transplantation after repair group (23.98% ± 1.75%) than in the other groups (P < .039); there was no significant difference in the other values. On the biomechanical test, the cell sheet transplantation after repair group (4 weeks after repair) showed significantly higher results than the other groups (P < .005). Conclusion: Our study shows that engineered stem cells are a clinically feasible stem cell delivery tool for rotator cuff repair. Clinical Relevance: This laboratory study provides evidence that ADSCs are effective in repairing RCTs, which are common sports injuries.

Obesity increases hepatic glycine dehydrogenase and aminomethyltransferase expression while dietary glycine supplementation reduces white adipose tissue in Zucker diabetic fatty rats.

Obesity is associated with altered glycine metabolism in humans. This study investigated the mechanisms regulating glycine metabolism in obese rats. Eight-week-old Zucker diabetic fatty rats (ZDF; a type-II diabetic animal model) received either 1% glycine or 1.19% L-alanine (isonitrogenous control) in drinking water for 6weeks. An additional group of lean Zucker rats also received 1.19% L-alanine as a lean control. Glycine concentrations in serum and liver were markedly lower in obese versus lean rats. Enteral glycine supplementation restored both serum and hepatic glycine levels, while reducing mesenteric and internal white fat mass compared with alanine-treated ZDF rats. Blood glucose and non-esterified fatty acid (NEFA) concentrations did not differ between the control and glycine-supplemented ZDF rats (P > 0.10). Both mRNA and protein expression of aminomethyltransferase (AMT) and glycine dehydrogenase, decarboxylating (GLDC) were increased in the livers of obese versus lean rats (P < 0.05). In contrast, glycine cleavage system H (GCSH) hepatic mRNA expression was downregulated in obese versus lean rats, although there was no change in protein expression. These findings indicate that reduced quantities of glycine observed in obese subjects likely results from an upregulation of the hepatic glycine cleavage system and that dietary glycine supplementation potentially reduces obesity in ZDF rats.

Adrenomedullin AttenuatesInflammation inWhite Adipose Tissueof Obese Rats Through Receptor-Mediated PKA Pathway.

ObjectiveAdrenomedullin (ADM) possesses therapeutic potential for inflammatory diseases. Consequently, the effects of ADM on inflammation in visceral white adipose tissue (vWAT) of obese rats or in adipocytes were explored in this study.MethodsMale rats were fed a high‐fat diet for 12 weeks to induce obesity, and obese rats were implanted with osmotic minipumps providing constant infusion of ADM (300 ng/kg per hour) and continued to be fed a high‐fat diet for 4 weeks.ResultsWhen compared with the control group, endogenous protein expression of ADM and ADM receptors in vWAT and in lipopolysaccharide (LPS)‐treated adipocytes was markedly increased. ADM significantly decreased the protein expression of the inflammatory mediators TNFα, IL‐1β, cyclooxygenase‐2, and inducible nitric oxide synthase in vWAT of obese rats and in adipocytes stimulated by LPS. It also inhibited the activation of the inflammatory signaling pathways MAPK and NF‐κB induced by LPS in adipocytes. These effects of ADM in adipocytes were inhibited by the administration of ADM receptor antagonist and cAMP‐dependent protein kinase (PKA) activation inhibitor.ConclusionsADM can inhibit inflammation in WAT in obesity, which may be mediated by the activation of ADM receptors and PKA.

Adipose-derived mesenchymal stem cells ameliorate the damages induced by arsenic trioxide in the testis of rats

Background: Arsenic trioxide is an element present everywhere in the environment. Aim: The current investigation planned to explain the remedial impacts of adipose mesenchymal stem cells (AD-MSCs) of rats against harmful impacts of Arsenic trioxide (As2O3; As III) on the testis of rats. Materials and Methods: Sixty male rats were divided into six groups: Group (1): served as the control without any treatments. Group (2): received a daily oral dose of HCL (0.5 mg/kg b.w). Experimental groups (3 and 4) received a low dose (3mg/kg b.w) of As III and groups (5,6) received a high dose (15 mg/kg b.w) of As III. The rats were sacrificed after 15 days in groups (3,5). Groups (4,6) were injected with (0.6×106) AD-MSCs / 0.5 ml PBS immediately after 15 days of oral doses of As III in low and high dose then sacrificed 7 days after MSCs injection. Results: The results indicated that AD-MSCs decreased the levels of p53 and Bax and increased the level of Bcl2. Additionally, treatment with AD-MSCs rescued the toxicity of low and high doses (L &H) As III induced change in TNF-α, IL-6, and IL-10 levels. In addition, As III L &H + AD-MSCs administration resulted in the gradual elevation of CD44 mRNA compared to control untreated mice. low and high doses of As III prompted histopathological damages in testis were they mostly turned around by treatment of AD-MSCs. Conclusion: The present results demonstrate that AD-MSCs got from the adipose tissue of rats can be a powerful treatment against harmfulness induced by As III in testis.

Irradiation of carotid baroreceptor with low-intensity pulsed ultrasound exerts different metabolic protection in perirenal, epididymal white adipose tissue and interscapular brown adipose tissue of obese rats.

This study was designed to clarify whether the irradiation of carotid baroreceptor (CB) with low-intensity pulsed ultrasound (LIPUS) protects against obesity by rebalancing the autonomic nervous system (ANS). Obesity was induced using a high-fat diet (HFD) for 8weeks in Sprague-Dawley rats. Irradiation with LIPUS was daily (20minutes a day) applied to the right CB. In our study, LIPUS significantly ameliorated metabolic disorders in obese rats. LIPUS partly restored norepinephrine (NE) and acetylcholine (ACH) levels in the perirenal white adipose tissue (PWAT), epididymal white adipose tissue (EWAT), interscapular brown adipose tissue (IBAT), and plasma of obese rats. LIPUS partially rectified the dysregulated AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor (PPAR) α/ɣ pathway in the PWAT, EWAT, and IBAT of obese rats. PPARγ and PPARγ target genes respond more sensitively to HFD and LIPUS in PWAT and EWAT than in IBAT. NE, ACH, uncoupling protein-1, phosphorylated AMPK, PPARα, and PPARα target genes respond more sensitively to HFD and LIPUS in IBAT than in PWAT and EWAT. Conclusion: LIPUS irradiation of CB exerts different metabolic protection in PWAT, EWAT, and IBAT by rebalancing the ANS and rectifying the AMPK/PPARα/ɣ pathway in obese rats.

Long-term nitrate administration increases expression of browning genes in epididymal adipose tissue of male type 2 diabetic rats

Expression of browning genes are lower in both humans and animals with type 2 diabetes (T2D). This study aims at determining effects of long-term nitrate administration on protein and mRNA levels of uncoupling protein 1 (UCP1), peroxisome proliferator activated receptor gamma (PPAR-γ), and PPAR-γ coactivator 1 alpha (PGC1-α) in epididymal adipose tissue (eAT) of rats with T2D. Male Wistar rats were divided into 4 groups (n = 6/group): Control, diabetes, control + nitrate (CN), and diabetes + nitrate (DN). T2D was induced using high fat diet combined with a low-dose of streptozotocin (30 mg/kg body weight). Sodium nitrate was administrated at a dose of 100 mg/L for 6 months in nitrate-treated rats. Fasting serum glucose and insulin concentrations were measured at months 0 (i.e. at start of the protocol), 3, and 6. At month 6, protein and mRNA levels of UCP1, PPAR-γ, and PGC1-α were measured in eAT samples. In addition, tissue concentration of cyclic guanosine monophosphate (cGMP) was measured and histological analyses were done at month 6. In rats with T2D, 6-month administration of nitrate decreased serum glucose and insulin concentrations by 13% and 23%, respectively and increased cGMP level by 85%. Rats with T2D had lower mRNA and protein levels of PPAR-γ (62%, P < 0.0001 and 18%, P = 0.0472), PGC1-α (49%, P = 0.0019 and 21%, P = 0.0482), and UCP1 (35%, P = 0.0613 and 30%, P = 0.0031) in eAT; 6-month nitrate administration restored these decreased levels to near control values. In addition, nitrate increased adipocyte density by 193% and decreased adipocyte area by 53% in rats with T2D. In conclusion, long-term low-dose nitrate administration increased mRNA and protein expressions of browning genes in white adipose tissue of male rats with T2D; these findings partly explain favorable metabolic effects of nitrate administration in diabetes.

Allergic Inflammation Alters microRNA Expression Profile in Adipose Tissue in the Rat.

Adipose tissue is a major source of circulating exosomal microRNAs (miRNAs) that are modulators of the immune response in various types of tissues and organs, including airways. Still, no evidence exists if allergic airway inflammation may affect fat tissue inflammation via alterations in the miRNA expression profile. Therefore, we investigated the miRNA expression profile in the adipose tissue upon induced allergic inflammation in the airways in the rat. Brown Norway rats were chronically sensitized to house dust mite extract for seven weeks. Body composition was performed using MiniSpec Plus. The eosinophil count and the total IgE level were determined to confirm the induction of allergic inflammation. MiRNA expression profiling was done using the next-generation sequencing with validation by qPCR. We found that allergic airway inflammation significantly increased fat in adipose tissue, glucose concentration, and the gene expression of adipose tissue-derived proinflammatory peptides (leptin, TNFα). In miRNA-seq analysis, we showed significant differences in the expression of 36 mature miRNAs, three precursors, and two miRNA families in adipose tissue of allergic rats. Two miRNAs—miRNA-151-5p and miRNA-423-3p—showed significantly increased expression in qPCR in adipose tissue and lungs of sensitized animals. Allergic airway inflammation affects fat tissue and alters miRNA expression profile in adipose tissue in the rat.

Effect of Eight Weeks of Aerobic Progressive Training with Capsaicin on Changes in PGC-1α and UPC-1 Expression in Visceral Adipose Tissue of Obese Rats With Diet

Objective: Decreased physical activity coupled with increased High‐Fat Diet (HFD) intake prompts obesity. Current research suggests that changing White Adipose Tissue (WAT) to brown promotes energy expenditure to counter obesity. The purpose of this study was to investigate the effects of aerobic Progressive training and Capsaicin (Cap) on Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and Uncoupling protein-1 (UPC-1) gene expression in rat fed a high-fat diet. Methods: 40 male Wistar rats aged 8-12 weeks, were fed a Normal Diet (ND) (n=8) or HFD (n=32) for 8 weeks. After 8 weeks, rats were divided into 5 groups: ND, HFD, High-Fat Diet-Training (HFDT), High-Fat Diet-Capsaicin (HFDCap), high-fat diet-training-capsaicin (HFDTCap). Training groups have performed a progressive aerobic running program on a motor-driven treadmill for eight weeks. Capsaicin (4 mg/kg/day) were administered orally, by gavage, once a day. PGC-1α and UCP-1 gene expression levels in the VAT were measured by Real-time PCR method. Results: The results of this study showed that PGC-1α and UCP-expression was decreased in HFD group compared to ND group. Also, the expression of PGC-1α and UPC-1 in HFDT, HFDCap and HFDTCap groups was significantly increased compared to HFD. The expression of PGC-1α and UPC-1 in HFDTCap was also significantly increased compared to HFDT and HFDCap groups. Conclusion: Possibly, eight weeks of progressive training combined with capsaicin administration has an effect on the browning of visceral adipose tissue in HFD rats by increasing expression of PGC-1α and UCP-1.

Adverse Effects of Methylglyoxal on Transcriptome and Metabolic Changes in Visceral Adipose Tissue in a Prediabetic Rat Model.

Excessive methylglyoxal (MG) production contributes to metabolic and vascular changes by increasing inflammatory processes, disturbing regulatory mechanisms and exacerbating tissue dysfunction. MG accumulation in adipocytes leads to structural and functional changes. We used transcriptome analysis to investigate the effect of MG on metabolic changes in the visceral adipose tissue of hereditary hypetriglyceridaemic rats, a non-obese model of metabolic syndrome. Compared to controls, 4-week intragastric MG administration impaired glucose tolerance (p < 0.05) and increased glycaemia (p < 0.01) and serum levels of MCP-1 and TNFα (p < 0.05), but had no effect on serum adiponectin or leptin. Adipose tissue insulin sensitivity and lipolysis were impaired (p < 0.05) in MG-treated rats. In addition, MG reduced the expression of transcription factor Nrf2 (p < 0.01), which controls antioxidant and lipogenic genes. Increased expression of Mcp-1 and TNFα (p < 0.05) together with activation of the SAPK/JNK signaling pathway can promote chronic inflammation in adipose tissue. Transcriptome network analysis revealed the over-representation of genes involved in insulin signaling (Irs1, Igf2, Ide), lipid metabolism (Nr1d1, Lpin1, Lrpap1) and angiogenesis (Dusp10, Tp53inp1).

Testosterone deficiency caused by castration increases adiposity in male rats in a tissue-specific and diet-dependent manner

BackgroundTestosterone deficiency in men is clinically associated with the development of metabolic syndrome, which manifests as obesity, hepatic steatosis, and type-2 diabetes. We investigated the effects of castration-induced testosterone deficiency on body adiposity and the expression of genes related to lipid metabolism and glucose uptake and androgen signaling in male rats fed a normal diet (ND) or a high-fat diet (HFD).MethodsChanges in lipid and glucose metabolism and androgen signaling were investigated at physiological and molecular levels in the muscle, liver, and adipose tissues of non-castrated and castrated rats under ND or HFD feeding.ResultsCastration-induced testosterone deficiency predisposed animals on ND to early development of fatty liver by activating fatty acid (FA) synthesis, whereas HFD activated hepatic FA uptake CD36 expression, leading to the development of hepatic steatosis. In rats fed ND, castration induced muscle fat accumulation by activating CD36 expression. In the subcutaneous fat of ND-fed rats, castration increased adiposity and the expression of FA synthesis-related genes, but it decreased glucose transporter gene expression. In the abdominal fat of rats fed ND, castration increased adiposity by upregulating FA synthesis-related genes, and HFD promoted adiposity by inducing FA uptake, glucose transporter, and FA synthesis-related gene expression. In rats fed ND, castration decreased body growth and muscle weight and downregulated the expression of genes androgen signaling in the longissimus dorsi muscle.ConclusionsTestosterone deficiency increases adiposity in a tissue-specific and diet-dependent manner. Testosterone deficiency decreases body and muscle weights and downregulates androgen signaling.