Rat Adipose Tissue Research Articles

Histology of skeletal muscle reconstructed by means of the implantation of autologous adipose tissue: an experimental study.

The purpose of this study was to determine the histological characteristics of a skeletal muscle reconstructed by means of the implantation of autologous adipose tissue following an experimentally-induced volumetric muscle loss. A cylindrical piece in the belly of the rat anterior tibial muscle was removed. In the hole, inguinal subcutaneous adipose tissue of the same rat was grafted. Animals were sacrificed 7, 14, 21, 28 and 60 days posttransplantation. Histological, histochemical, immunohistochemical and morphometric techniques were used. At all times analyzed, the regenerative muscle fibers formed from the edges of the muscle tissue showed histological, histochemical and immunohistochemical differences in comparison with the control group. These differences are related to delays in the maturation process and are related to problems in reinnervation and disorientation of muscle fibers. The stains for MyoD and desmin showed that some myoblasts and myotubes seem to derive from the transplanted adipose tissue. After 60 days, the transplant area was 20% occupied by fibrosis and by 80% skeletal muscle. However, the neo-muscle was chaotically organized showing muscle fiber disorientation and centronucleated fibers with irregular shape and size. Our results support the hypothesis that, at least from a morphological point of view, autologous adipose tissue transplantation favors reconstruction following a volumetric loss of skeletal muscle by combining the inherent regenerative response of the organ itself and the myogenic differentiation of the stem cells present in the adipose tissue. However, in our study, the formed neo-muscle exhibited histological differences in comparison with the normal skeletal muscle.

High dietary oleic acid in olive oil-supplemented diet enhanced omega-3 fatty acid in blood plasma of rats.

This study was conducted to investigate the effect of dietary oleic acid in olive oil‐supplemented diets on the blood lipid profile and fatty acid composition in blood plasma and adipose tissue of rats. A total of 60 Sprague Dawley rats with mean body weight of 249 g ± 3.04 g were equally divided into three diet groups: control (CON) contained 10% coconut oil, olive50 contained 5% coconut oil and 5% olive oil, and olive100 contained 10% olive oil. Oleic acid (OA) level was highest in olive100 followed by the olive50 and control. The final body weight (BW) of the rats was significantly affected by the intake of OA, in which rats fed olive100 had the lowest final BW, which signified that OA could be associated with weight loss. Olive oil intake significantly increased levels of the high‐density lipoprotein cholesterol (HDL‐C) and exhibited a potential attenuation effect on the glutamic‐oxaloacetic transaminase and the glutamic‐pyruvic transaminase, and a potential role in the reduction of triglycerides in the bloodstream of the animals. In terms of fatty acid composition, significantly high OA was observed in the blood plasma and adipose tissues of rats fed olive100. Omega‐3 polyunsaturated fatty acids (PUFAs), such as linolenic (C18:3 n−3), eicosapentaenoic (C20:5 n−3), and docosahexaenoic (C22:6 n−3), and n−6 PUFA arachidonic (C20:4 n−6) were also significantly increased in the blood plasma of rats fed olive100. These findings suggest that the intake of dietary high OA may enhance the omega‐3 fatty acid levels in the blood plasma of rats and may have a positive effect in reducing risks to cardiovascular disease, as evidenced by weight loss, increased HDL‐C levels, and decreased TG levels in the blood plasma of experimental animals.

Maternal low protein diet induces persistent expression changes in metabolic genes in male rats.

BACKGROUNDPerinatal exposure to a poor nutritional environment predisposes the progeny to the development of metabolic disease at the adult age, both in experimental models and humans. Numerous adaptive responses to maternal protein restriction have been reported in metabolic tissues. However, the expression of glucose/fatty acid metabolism-related genes in adipose tissue and liver needs to be described.AIMTo evaluate the metabolic impact of perinatal malnutrition, we determined malnutrition-associated gene expression alterations in liver and adipose tissue.METHODSIn the present study, we evaluated the alterations in gene expression of glycolytic/Krebs cycle genes (Pyruvate dehydrogenase kinase 4 and citrate synthase), adipogenic and lipolytic genes and leptin in the adipose tissue of offspring rats at 30 d and 90 d of age exposed to maternal isocaloric low protein (LP) diet throughout gestation and lactation. We also evaluated, in the livers of the same animals, the same set of genes as well as the gene expression of the transcription factors peroxisome proliferator-activated receptor gamma coactivator 1, forkhead box protein O1 and hepatocyte nuclear factor 4 and of gluconeogenic genes.RESULTSIn the adipose tissue, we observed a transitory (i.e., at 30 d) downregulation of pyruvate dehydrogenase kinase 4, citrate synthase and carnitine palmitoyl transferase 1b gene expression. Such transcriptional changes did not persist in adult LP rats (90 d), but we observed a tendency towards a decreased gene expression of leptin (P = 0.052). The liver featured some gene expression alterations comparable to the adipose tissue, such as pyruvate dehydrogenase kinase 4 downregulation at 30 d and displayed other tissue-specific changes, including citrate synthase and fatty acid synthase upregulation, but pyruvate kinase downregulation at 30 d in the LP group and carnitine palmitoyl transferase 1b downregulation at 90 d. These gene alterations, together with previously described changes in gene expression in skeletal muscle, may account for the metabolic adaptations in response to maternal LP diet and highlight the occurrence of persistent transcriptional defects in key metabolic genes that may contribute to the development of metabolic alterations during the adult life as a consequence of perinatal malnutrition.CONCLUSIONWe conclude that perinatal malnutrition relays long-lasting transcriptional alterations in metabolically active organs, i.e., liver and adipose tissue.

Cooperative effects of galanin and leptin on alleviation of insulin resistance in adipose tissue of diabetic rats.

It was reported that either orexigenic neuropeptide galanin or anorexigenic hormone leptin caught benefit insulin sensitivity through increasing the translocation of glucose transporter 4 (GLUT4) in patients with diabetes. To date, it is unknown whether galanin can potentiate the effect of leptin on alleviation of insulin resistance. Therefore, in the current study we sought to assess the combined effect of central leptin and galanin on insulin resistance in the adipose tissues of type 2 diabetic rats. Galanin and leptin were injected into the intracerebroventricle of the diabetic rats, respectively, or cooperatively once a day for 2 weeks. Then, several indexes of insulin resistance were examined. The results showed that glucose infusion rates in the hyperinsulinaemic‐euglycaemic clamp test, plasma adiponectin content and GLUT4 translocation, as well as Akt phosphorylation in fat cells, were higher, not GLUT4 protein and GLUT4 mRNA expression, but HOMA index was lower in the galanin + leptin group than either one of them. Furthermore, treatment with MK‐2206, an Akt inhibitor, blocked the combined effects of galanin + leptin on alleviation of insulin resistance. These results suggest that galanin can improve the leptin‐induced mitigative effects on insulin resistance in the fat cells, and those provided new insights into the potential tactics for prevention and remedy of insulin resistance.

SAT-LB108 Brown Adipose Tissue Activity in Different Insulin Resistance Models in Rats: Lean Goto-Kakizaki and Diet-Induced Obese Wistar Rats

Obesity is growing worldwide and one of the main causes of death. It is highly associated with the development of type 2 diabetes mellitus, insulin resistance, cardiovascular disease, metabolic syndrome, and certain forms of cancer. The presence of two types of adipose tissue, which have the opposing function, has been known for a long time. White adipose tissue (WAT) is the tissue of energy expenditure storage, while Brown adipose tissue (BAT) is characterized to dissipates energy as heat and is required for non-shivering thermoregulation, presents a high thermogenesis capacity, regulating systemic metabolism and participating of the glycemic homeostasis, and displayed a high metabolic activity, which is due the presence of UCP1 (uncoupling protein-1) and through this the ability to dissipate energy, to burn away (extra) food, and it had been a proposal as a potential target to obesity treatment. Was identification a novel type of adipocytes, brite/beige adipocytes, localized within the WAT depots and possess the ability to increase energy expenditure. The BAT activity is regulated by the adrenergic receptor and Sympathetic Nervous System; however, its regulation by the insulin resistance state is not completely elucidated yet. In this study, we evaluated the BAT activity and response different animal models of insulin resistance: lean type 2 diabetic Goto-Kakizaki rats and high-fat diet-induced obese Wistar rats. Animals at eight weeks-old were fed ad libitum with a control diet (Wistar-Control and GK-CD), high-fat diet (Wistar-HFD) and/ or plus condensed milk (wistar-HFD+CM) for eight weeks. To evaluate the BAT activity, 18F-FDG small-animal PET/CT was performed at 30 min after CL316,243 or saline injection. The activity of brown adipose tissue by 18F-FDG uptake sob basal conditions, when injecting saline, not shown a significant difference between the groups, however, shown lower 18F-FDG uptake in animals GK than compared with other groups. After CL 316,243 stimuli a highly specific beta 3- adrenoceptor agonist, the animals GK showed decreased 18F-FDG uptake in brown adipose tissue than the control group (by 56%). The analyze between to the groups sob saline or CL 316, 243 conditions by two-way ANOVA test, showed after stimuli that control group showed increased 18F-FDG uptake when compared to the HFD +CM and GK (by 68,9%) and (by 71%), respectively. The GK animals showed lower 18F-FDG uptake when compared with HFD and HFD+CM groups (by 62,3%) and (by 51%). The 18F-FGD showed decreased BAT activity after CL316,243 stimuli in GK animals. The encephalon18F-FDG uptake, under saline, showed higher uptake the animals HFD when compared with the GK group (by 171,3%). After stimuli CL 316, 243, the HFD group displayed higher 18F-FDG uptake than CM+HFD group and control group (by 35,3%) and (by 56,2%), respectively. The analyze between groups, baseline or CL 316, 243, showed that the baseline the HFD group displayed higher 18F-FDG uptake when compared with GK and CM+HFD group (by 63,1%) and (by 73,4%), respectively. These data showed decreased 18F-FDG uptake in response the stimuli CL 316, 243 in all groups, except GK group. These findings suggest a transition from brown to white adipose tissue in GK rats, a process known as “whitening”.

Effects of leptin on lipid metabolism and inflammatory factors in diabetic rats

Objective: To investigate the effects of leptin on glucose metabolism and related inflammatory factors in diabetic rats. Methods: Ten healthy male Wistar rats were randomly selected as the control group. Fifty rats were fed with high sugar and high fat diet and injected with streptozotocin (STZ, 25 mg/kg) intraperitoneally. They were randomly divided into model group, leptin low, middle and high dose group. The rats in the low, middle and high dose group were fed with leptin at the doses of 20, 50 and 100 μg/kg for 5 d respectively. Blood glucose (FBG) was measured by GOD-PAP method, insulin content (INS) was tested by radioimmunoassay, the serum levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) were determined by automatic biochemical analyzer, the contents of malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the expression of leptin in adipose tissue of diabetic rats. Results: Compared with the control group, the blood glucose levels of other groups were increased significantly (P＜0.01). Compared with the model group, the blood glucose levels of middle and high dose leptin rats decreased significantly (P＜0.05, P＜0.01). The insulin level of high dose leptin group decreased significantly (P＜0.01). There was no significant difference in FBG and INS among the three groups (P＞0.05). Compared with the model group, TC levels of middle and high dose leptin group were decreased significantly (P＜0.05, P＜0.01). TG and LDL-C levels of high dose leptin group were decreased significantly (P＜0.05), HDL-C level of high dose group was increased significantly (P＜0.01). Compared with different dose groups, the high dose of leptin (100 μg/kg) could decrease the levels of TC, TG and LDL-C, and increase the level of HDL-C, which was better than those of the middle and low dose of leptin (P＜0.05) Compared with the model group (52.27±10.93), the levels of leptin in low, middle and high dose group were (47.35±12.09), (44.68±10.23) and (40.13±9.87) respectively, which could be decreased by leptin in a dose-dependent manner. Conclusion: The abnormal secretion of leptin is one of the factors inducing diabetes mellitus. Under the intervention of a certain concentration of exogenous leptin (100 μg/kg), it can significantly reduce the level of MDA, TNF-α, and improve the level of IL-6. The mechanism may be closely related to the reduction of inflammatory response, oxidative stress and correction of dyslipidemia. Leptin also reduces the risk of disease progression in diabetes treatment.

Experimental Study of the Possibility of Culturing of Mesenchymal Stromal Cell and Induction of Osteogenic Differentiation on Collagen-Based Scaffolds of Various Modifications.

We analyzed the suitability of various collagen-based scaffolds for culturing and osteogenic differentiation of mesenchymal stromal cells (MSC). Decellularized and lyophilized swine intestinal submucosa (SIS) and porous collagen sponge made from reconstructed bovine derma (PCS) were the most effective in promoting MSC adhesion, survival, and growth. MSC from rat and mouse bone marrow and rat adipose tissue successfully adhered to the scaffold surface and penetrated into its deep layers. These scaffolds were also the most effective in inducing osteogenesis. These results indicate that microarchitectonics of PCS and SIS is optimal for support of MSC growth and osteogenic differentiation.

Nicotine exposure during breastfeeding reduces sympathetic activity in brown adipose tissue and increases in white adipose tissue in adult rats: Sex-related differences

Nicotine transfer via breast milk induces obesity in the adult offspring. We hypothesize that sympathetic nervous system (SNS) activity, brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) lipogenesis/adipogenesis are altered in adult rats that were exposed to nicotine exclusively during the breastfeeding period. Lactating Wistar rats were separated into two groups: nicotine (NIC), dams implanted with osmotic minipumps containing 6 mg/kg of nicotine at postnatal day (PN) 2; control, dams were implanted with saline-containing minipumps. Euthanasia occurred at PN120 or PN180. NIC offspring had lower BAT SNS activity and higher BAT lipid content. NIC males showed lower UCP1, β3-AR and CPT1a, while NIC females showed lower UCP1, TRα1, CPT1a, suggesting lower thermogenesis. NIC males showed higher WAT SNS activity, WAT β3-AR, adrenal catecholamine, FAS, PPARγ and adipocytes area, while NIC females showed higher ACC, FAS, CEBPβ and PPARγ. These findings indicate increased lipogenesis/adipogenesis in both sexes, with a possible compensatory sympathetic activated-lipolysis in males. NIC males had higher hypothalamic pAMPK/AMPK, explaining the lower BAT sympathetic activity. Neonatal nicotine exposure reduces BAT SNS activity and thermogenesis, and, only in males, increases WAT adipogenesis/lipogenesis, despite higher WAT SNS activity. These alterations can be associated with obesogenesis in this programming model.

PuraMatrix hydrogel enhances the expression of motor neuron progenitor marker and improves adhesion and proliferation of motor neuron-like cells.

Objective(s):Cell therapy has provided clinical applications to the treatment of motor neuron diseases. The current obstacle in stem cell therapy is to direct differentiation of stem cells into neurons in the neurodegenerative disorders. Biomaterial scaffolds can improve cell differentiation and are widely used in translational medicine and tissue engineering. The aim of this study was to compare the efficiency of two-dimensional with a three-dimensional culture system in their ability to generate functional motor neuron-like cells from adipose-derived stem cells. Materials and Methods:We compared motor neuron-like cells derived from rat adipose tissue in differentiation, adhesion, proliferation, and functional properties on two-dimensional with three-dimensional culture systems. Neural differentiation was analyzed by immunocytochemistry for immature (Islet1) and mature (HB9, ChAT, and synaptophysin) motor neuron markers. Results:Our results indicated that the three-dimensional environment exhibited an increase in the number of Islet1. In contrast, two-dimensional culture system resulted in more homeobox gene (HB9), Choline Acetyltransferase (ChAT), and synaptophysin positive cells. The results of this investigation showed that proliferation and adhesion of motor neuron-like cells significantly increased in three-dimensional compared with two-dimensional environments. Conclusion:The findings of this study suggested that three-dimension may create a proliferative niche for motor neuron-like cells. Overall, this study strengthens the idea that three-dimensional culture may mimic neural stem cell environment for neural tissue regeneration.

The Effect of 6 Weeks Aerobic Training and Aqueous Extract of Caraway Seed (Carum Carvi) on the Expression of CTRP12 Gene, Body Weight Changes and Subcutaneous Adipose Tissue in Obese Male Rats: An Experimental Study

The Effect of 6 Weeks Aerobic Training and Aqueous Extract of Caraway Seed (Carum Carvi) on the Expression of CTRP12 Gene, Body Weight Changes and Subcutaneous Adipose Tissue in Obese Male Rats: An Experimental Study

Western Diet‐Induced Hypertension involves HMGB1/TLR4 Signaling in Perivascular Adipose Tissue of Female Rats

BackgroundOverconsumption of a Western Diet (WD), a high‐fat and high‐sugar diet, is a major factor implicated in rising obesity rates in the US. Perivascular adipose tissue (PVAT) possesses a vasculo‐protective role. In obesity, PVAT expands and becomes inflamed, contributing to vascular complications. High motility group box 1 (HMGB1), a cytokine, has been demonstrated to mediate vascular inflammation. Recent studies also suggest that PVAT plays a role in obesity‐related hypertension; however, the underlying mechanisms are still not well understood. We hypothesize that WD increases HMGB1 production in PVAT which in turn activates Toll‐like receptor 4 (TLR4) signaling in an autocrine/paracrine manner, resulting in hypertension.MethodsWe have established a model of WD‐induced hypertension in female rats. Adult female Wistar rats (n= 9) were randomized into two groups. Control Group (n= 4) received a regular chow diet (5% fat, 48.7% carbohydrates [3.2% sucrose], and 24.1% protein) and WD group (n= 5) received WD (40% fat, 43% carbohydrates [34% sucrose], and 17% protein) for 28 weeks. Metabolic parameters (body weight, body mass index (BMI), triglycerides, and non‐esterified free fatty acids [NEFA]) were assessed. Arterial blood pressure was measured via carotid catherization at the end of the experimental protocol. Thoracic aortas with PVAT were obtained for vascular studies and molecular assays. Vascular studies were performed using a wire myograph to assess vasodilatory responses.ResultsBody weight (358.9 ± 10.2 vs 270.1 ± 12.3g controls, p<0.005) and BMI (0.68 ± 0.02 vs. 0.06 ± 0.03 g/cm2controls, p<0.005) were increased in the WD group, confirming obesity. The WD group also demonstrated increased serum triglycerides (49.8 ± 4.7 vs. 14.3 ± 1.8mg/dL controls, p<0.05) and NEFA (0.57 ± 0.02 vs. 0.79 ± 0.04 mM controls, p<0.05). WD increased systolic blood pressure (144.04 ± 2.8 vs. 115.1 ± 3.9 mmHg controls, p<0.001), diastolic blood pressure (108.3 ± 3.1 vs. 89.5 ± 4.3 mmHg controls, p<0.01), and heart rate (386.1 ± 8.8 vs. 307.7 ± 40.3 bpm controls, p<0.05). Impaired vasodilation in the WD group in comparison to controls was worsened in the presence of PVAT, suggesting dysfunctional PVAT. Histological analysis of PVAT revealed a switch from brown‐like adipose tissue to white‐like adipose tissue, along with a significant decrease in uncoupling protein 1 (UCP‐1) expression (1.5‐fold decreased, p<0.05), a marker of thermogenesis. An oxidative/inflammatory state in the PVAT was confirmed by a 50% increase in reactive oxygen species levels (p<0.01). Strikingly, the novelty of this study revealed increased HMGB1 expression (2.0‐fold increased, p<0.05) along with increased TLR4 expression (2.5‐fold increased, p<0.05) in the PVAT of the WD group.ConclusionOur findings suggest that upregulated HMGB1/TLR4 signaling in the PVAT may induce a local inflammatory response through an autocrine/paracrine manner in the vasculature, contributing to dysregulation of blood pressure in the context of obesity.Support or Funding InformationNIH

The Impact of Moderate-Intensity Continuous or High-Intensity Interval Training on Adipogenesis and Browning of Subcutaneous Adipose Tissue in Obese Male Rats.

This study compares the effect of two types of exercise training, i.e., moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT) on the browning of subcutaneous white adipose tissue (scWAT) in obese male rats. Effects on fat composition, metabolites, and molecular markers of differentiation and energy expenditure were examined. Forty male Wistar rats were assigned to lean (n = 8) or obese (n = 32) groups and fed either a standard chow or high-fat obesogenic diet for 10 weeks. Eight lean and obese rats were then blood and tissue sampled, and the remaining obese animals were randomly allocated into sedentary, MICT, or HIIT (running on a treadmill 5 days/week) groups that were maintained for 12 weeks. Obesity increased plasma glucose and insulin and decreased irisin and FGF-21. In scWAT, this was accompanied with raised protein abundance of markers of adipocyte differentiation, i.e., C/EBP-α, C/EBP-β, and PPAR-γ, whereas brown fat-related genes, i.e., PRDM-16, AMPK/SIRT1/PGC-1α, were reduced as was UCP1 and markers of fatty acid transport, i.e., CD36 and CPT1. Exercise training increased protein expression of brown fat-related markers, i.e., PRDM-16, AMPK/SIRT1/PGC-1α, and UCP1, together with gene expression of fatty acid transport, i.e., CD36 and CPT1, but decreased markers of adipocyte differentiation, i.e., C/EBP-α, C/EBP-β, and plasma glucose. The majority of these adaptations were greater with HIIT compared to MICT. Our findings indicate that prolonged exercise training promotes the browning of white adipocytes, possibly through suppression of adipogenesis together with white to beige trans-differentiation and is dependent on the intensity of exercise.

Effect of chronic exposure to monocrotophos on white adipose tissue in rats and its association with metabolic dyshomeostasis.

Earlier, we demonstrated that chronic exposure to monocrotophos (MCP) elicits insulin resistance in rats along with increased white adipose tissue (WAT) weights. This study was carried out to delineate the biochemical and molecular changes in adipose tissues of rats subjected to chronic exposure to MCP (0.9 and 1.8 mg/kg bw/d for 180 days). Pesticide-treated rats exhibited increased fasting glucose and hyperinsulinemia as well as dyslipidemia. Tumor necrosis factor-alpha and leptin levels were elevated, while adiponectin level was suppressed in plasma of treated rats. MCP treatment caused discernable increase in the weights of perirenal and epididymal WAT. Acetyl coenzyme A carboxylase, fatty acid synthase, glyceraldehyde-3-phosphate dehydrogenase, lipin-1, and lipolytic activities were elevated in the WAT of MCP-treated rats. Corroborative changes were observed in the expression profile of proteins that are involved in lipogenesis and adipose tissue differentiation. Our results clearly demonstrate that long-term exposure to organophosphorus insecticides (OPIs) such as MCP has far-reaching consequences on metabolic health as evidenced by the association of adipogenic outcomes with insulin resistance, hyperinsulinemia, endocrine dysregulations, and dyslipidemia. Taken together, our results suggest that long-term exposure to OPI may be a risk factor for metabolic dysregulations.

Oral L-glutamine restores adenosine and glutathione content in the skeletal muscle and adipose tissue of insulin-resistant pregnant rats.

Mishandling of lipid and glycogen has been documented as a feature of metabolic tissues in insulin resistance-related disorders. However, reports exist detailing that L-glutamine (GLN) protects non-adipose tissue against the deleterious effects of metabolic disorders. Therefore, we hypothesized that GLN would protect skeletal muscle and adipose tissue against the deleterious effects of lipid and glycogen mishandlings by increasing adenosine and glutathione levels in pregnant rats exposed to fructose (FRU)-enriched drinks. Pregnant Wistar rats weighing 150 to 180 g were randomly assigned to control, GLN, FRU, and FRU + GLN groups (six rats/group). The groups received vehicle (P.o.), glutamine (1 g/kg), FRU (10%; w/v), and FRU + GLN, respectively, for 19 d. Data show that FRU caused insulin resistance with corresponding increased blood glucose, circulating and pancreatic insulin levels, and lipid accumulation and glycogen depletion in skeletal muscle, but glycogen accumulation and a decreased lipid profile in adipose tissue. Adenosine and glutathione content decreased, whereas adenosine deaminase, xanthine oxidase, uric acid, and malondialdehyde concentrations increased in both tissues. In addition, glucose-6-phosphate dehydrogenase activity decreased in skeletal muscle but remained unaltered in adipose tissue. However, supplementation with GLN improved perturbed lipid and glycogen with a corresponding increase in adenosine and glutathione. The present results collectively indicate that lipid and glycogen mishandlings caused by high gestational FRU intake result in the depletion of adenosine and glutathione in skeletal muscle and adipose tissue. These findings also suggest that L-glutamine protects against skeletal muscle and adipose tissue dysmetabolism by enhancing adenosine and glutathione.

Pilot study and bioinformatics analysis of differentially expressed genes in adipose tissues of rats with excess dietary intake.

Excessive adipose tissue accumulation is an increasing health problem worldwide. The present study aimed to determine differentially expressed genes (DEGs) that are associated with the excessive accumulation of adipose tissues by PCR arrays in an excess dietary intake animal model. For this purpose, male Sprague Dawley rats were randomly assigned to 2 groups: Control (given an ordinary diet) and experimental (given twice the amount of the ordinary diet). After 2 months of feeding, the abdominal cavities of the rats from each group were opened, then subcutaneous and visceral adipose tissues were removed. The adipose tissues collected were then used for total RNA extraction and then reverse transcribed to cDNA, which was then used as a template to identify the DEGs of 84 transcripts for rat obesity by RT2 Profiler PCR Arrays. The results showed significant downregulation of bombesin-like receptor 3 (BRS3) and uncoupling protein 1 (UCP1) in visceral adipose tissues of experimental rats compared with those of the control rats, and differential gene expression analysis showed an association with fat cell differentiation and regulation of triglyceride sequestration, as well as fatty acid binding. The gene expression patterns observed in the present study, which may be associated with peroxisome proliferator-activated receptor-γ (PPARG) on excessive visceral adipose tissue accumulation, may be useful in identifying a group of surrogate biomarkers for the early diet-induced accumulation of visceral adipose tissue detection in humans. The biomarkers can also be the specific targets for drug development to reduce excessive visceral adipose tissue accumulation in the body and its associated diseases.

High-Intensity Interval Training Reversed High-Fat Diet-Induced M1-Macrophage Polarization in Rat Adipose Tissue via Inhibition of NOTCH Signaling.

IntroductionThere is accumulating evidence on the beneficial effect of exercise intervention in the management of metabolic disorders; however, the molecular mechanism is still unclear. Here, the current study aimed to compare the effect of high-intensity interval training (HIIT) and continuous endurance training (CET) on serum and adipose-tissue markers of M1/M2 macrophage polarization.MethodsA total of 45 healthy male Wistar rats were divided into groups of normal chow (n=10) and high-fat diet (HFD) (n=35). Then, rats receiving the HFD were randomly divided into four groups. Training programs were performed for 5 days/week over 10 weeks. The CET protocol included 30 minutes running at 50%–60% of VO2max. The HIIT protocol consisted of five repeated intervals of 2-minute sprints on the treadmill at 80%–90% VO2max workload with 1 minute's 30%–35% VO2max interval for each rat. Then, biochemical parameters were assessed. Macrophage-polarization markers were assessed at mRNA and protein levels by real-time PCR and Western blotting, respectively.ResultsBoth exercise-training programs, especially HIIT, reversed increased serum biochemical parameters (glucose, triglycerides, cholesterol, Homeostatic Model Assessment of Insulin Resistance, and hsCRP), M1-polarization markers (circulating IL6, TNFα, and adipose-tissue mRNA expression of IL6, TNFα and iNOS), M2 markers (CD206, CD163, and IL10 expression), as well as pIκKB, pNFκB, and NICD expression in HFD-induced diabetes.ConclusionOur findings suggest that despite devoting less time, the HIIT workout is a more effective intervention for diabetes management. Moreover, HIIT reverses HFD-induced macrophage polarization by targeting the NFκB and NOTCH signaling pathways.

Resveratrol ameliorates inflammatory and oxidative stress in type 2 diabetic Goto-Kakizaki rats

Type 2 diabetes is associated with inflammatory and oxidative stress. Resveratrol, a naturally occurring diphenolic compound, was shown to improve glycemic control and alleviate metabolic disturbances in Goto-Kakizaki (GK) rats, a non-obese model of type 2 diabetes. However, in GK rats effects of resveratrol addressing inflammatory and oxidative stress were not explored. The present study aimed to determine anti-inflammatory and anti-oxidative properties of resveratrol in these rats. GK and Sprague-Dawley (SD) rats were divided into 4 groups: GK control, GK treated with resveratrol, SD control and SD treated with resveratrol. Resveratrol (20 mg/kg b.w.) was given once a day for 10 weeks. It was shown that contents of inflammatory markers, interleukin 6 (IL-6), interleukin 1 β (IL-1β), tumor necrosis factor α (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), were increased in the skeletal muscle of diabetic rats, but these effects were prevented by resveratrol therapy. Similarly, amounts of IL-1β and TNF-α were elevated in livers of GK rats; however, this rise was alleviated in resveratrol-treated animals. Moreover, the contents of inflammation-related factors (IL-6, IL-1β, TNF-α and NF-κB) were augmented in adipose tissue of GK rats; nevertheless, in this tissue resveratrol was ineffective. Resveratrol reduced also lipid peroxidation in the skeletal muscle, reduced activities of glutathione peroxidase in blood serum and catalase in the livers of GK rats. Our new findings show that resveratrol therapy results in relieving inflammatory and oxidative stress in GK rats, which may be largely associated with the alleviation of metabolic disturbances in this model of diabetes. Nevertheless, it was demonstrated that the efficacy of resveratrol action is tissue-specific.

Inorganic Nitrate Promotes Glucose Uptake and Oxidative Catabolism in White Adipose Tissue Through the XOR-Catalyzed Nitric Oxide Pathway.

An aging global population combined with sedentary lifestyles and unhealthy diets has contributed to an increasing incidence of obesity and type 2 diabetes. These metabolic disorders are associated with perturbations to nitric oxide (NO) signaling and impaired glucose metabolism. Dietary inorganic nitrate, found in high concentration in green leafy vegetables, can be converted to NO in vivo and demonstrates antidiabetic and antiobesity properties in rodents. Alongside tissues including skeletal muscle and liver, white adipose tissue is also an important physiological site of glucose disposal. However, the distinct molecular mechanisms governing the effect of nitrate on adipose tissue glucose metabolism and the contribution of this tissue to the glucose-tolerant phenotype remain to be determined. Using a metabolomic and stable-isotope labeling approach, combined with transcriptional analysis, we found that nitrate increases glucose uptake and oxidative catabolism in primary adipocytes and white adipose tissue of nitrate-treated rats. Mechanistically, we determined that nitrate induces these phenotypic changes in primary adipocytes through the xanthine oxidoreductase-catalyzed reduction of nitrate to NO and independently of peroxisome proliferator-activated receptor-α. The nitrate-mediated enhancement of glucose uptake and catabolism in white adipose tissue may be a key contributor to the antidiabetic effects of this anion.

Quercetin attenuates adipose hypertrophy, in part through activation of adipogenesis in rats fed a high-fat diet

An impaired capacity of adipose tissue expansion leads to adipocyte hypertrophy, inflammation and insulin resistance (IR) under positive energy balance. We previously showed that a grape pomace extract, rich in flavonoids including quercetin (Q), attenuates adipose hypertrophy. This study investigated whether dietary Q supplementation promotes adipogenesis in the epididymal white adipose tissue (eWAT) of rats consuming a high-fat diet, characterizing key adipogenic regulators in 3T3-L1 pre-adipocytes. Consumption of a high-fat diet for 6 weeks caused IR, increased plasma TNFα concentrations, eWAT weight, adipocyte size and the eWAT/brown adipose tissue (BAT) ratio. These changes were accompanied by decreased levels of proteins involved in angiogenesis, VEGF-A and its receptor 2 (VEGF-R2), and of two central adipogenic regulators, i.e. PPARγ and C/EBPα, and proteins involved in mature adipocyte formation, i.e. fatty acid synthase (FAS) and adiponectin. Q significantly reduced adipocyte size and enhanced angiogenesis and adipogenesis without changes in eWAT weight and attenuated systemic IR and inflammation. In addition, high-fat diet consumption increased eWAT hypoxia inducible factor-1 alpha (HIF-1α) levels and those of proteins involved in adipose inflammation (TLR-4, CD68, MCP-1, JNK) and activation of endoplasmic reticulum (ER) stress, i.e. ATF-6 and XBP-1. Q mitigated all these events. Q and quercetin 3-glucoronide prevented TNFα-mediated downregulation of adipogenesis during 3T3-L1 pre-adipocytes early differentiation. Together, Q capacity to promote a healthy adipose expansion enhancing angiogenesis and adipogenesis may contribute to reduced adipose hypertrophy, inflammation and IR. Consumption of diets rich in Q could be useful to counteract the adverse effects of high-fat diet-induced adipose dysfunction.

Effect of Fresh Red radish Roots Juice on some Biomarker for hypertrophy of adipose tissue in Obese Rats

R ecently, red radish sparked much interest in health and nutrition. So this study aimed to clarify the effect of red radish roots juice on obese rats. The chemical analysis of the phenolic content and antioxidant activity of the red radish roots juice were determined. An experiment performed on 36 male rats distributed into 6 equal groups. The first group kept as normal control, fed on a basal diet. While other groups fed on a high-fat diet to induce obesity. Obese rats, group (2) left as a positive control. Three obese groups (3, 4 and 5) received red radish roots juice (1, 2 and 3 ml/kg BW/ day) with a high fat-diet. After 6 weeks, biological parameters (feed intake FI, bodyweight gain BWG, body mass index BMI, and Feed efficiency ratio FER) calculated, and biochemical analysis (serum leptin, adiponectin, oxidative stress, tumor necrosis factor-alpha (TNFα), total antioxidant capacity, and lipid profile) estimated. Results confirmed that a high level of ferric reducing antioxidant (FRAP) and total radical-trapping antioxidant parameter (TRAP) in a positive control group. Red radish roots juice affected a significant decrease in leptin, adiponectin, TNF-α, and total oxidant capacity; while increasing the total antioxidant capacity as compared to the positive control group. Also, lipid profile normalization showed in group 5 that received a high-fat diet plus 3 ml red radish roots juice. Therefore, this study concluded that the consumption of red radish as a functional food for a delay may protect the risk of adipose tissue.