Obese Diabetic Rats Research Articles

Cornelian Cherry Pulp Has Beneficial Impact on Dyslipidemia and Reduced Bone Quality in Zucker Diabetic Fatty Rats.

Simple SummaryFruits of Cornelian cherry (Cornus mas L.) are often used as an antidiabetic supplement mainly due to their hypoglycemic properties. A very important aspect and secondary complication of type 2 diabetes mellitus (T2DM) represents diabetic bone disease. In our study, the impacts of Cornus mas pulp on lipid profile and bone quality parameters were evaluated in Zucker diabetic fatty (ZDF) rats as a well-matched T2DM animal model. We demonstrated, for the first time, that Cornelian cherry pulp could be used as a potential therapeutic agent to alleviate T2DM-reduced bone quality and impaired bone health. Moreover, the hypolipidemic effect of this fruit was also confirmed in our study.Cornelian cherry (Cornus mas L.) is a medicinal plant with a range of biological features. It is often used as a nutritional supplement in the treatment of diabetes mellitus. Our study was aimed to first investigate the effects of Cornelian cherry pulp on bone quality parameters in Zucker diabetic fatty (ZDF) rats. Moreover, lipid-lowering properties of this fruit were also evaluated. Adult rats (n = 28) were assigned into four groups of seven individuals each: L group (non-diabetic lean rats), C group (diabetic obese rats), and E1 and E2 groups (diabetic obese rats receiving 500 and 1000 mg/kg body weight of Cornelian cherry pulp, respectively, for 10 weeks). Significantly lower levels of triglyceride, total cholesterol and alkaline phosphatase activity were determined in the E2 group versus the C group. A higher dose of Cornus mas also had a beneficial impact on femoral weight, cortical bone thickness, relative volume of trabecular bone and trabecular thickness. We observed elevated density of Haversian systems and accelerated periosteal bone apposition in both treated groups (E1 and E2). Our results clearly demonstrate that Cornelian cherry pulp has a favorable effect on lipid disorder and impaired bone quality consistent with type 2 diabetes mellitus in a suitable animal model.

Serum glucose excretion after Roux-en-Y gastric bypass: a potential target for diabetes treatment

ObjectiveThe mechanisms underlying type 2 diabetes resolution after Roux-en-Y gastric bypass (RYGB) are unclear. We suspected that glucose excretion may occur in the small bowel based on observations in humans....

Sleeve Gastrectomy Ameliorates Diabetes-Related Spleen Damage by Improving Oxidative Stress Status in Diabetic Obese Rats.

Oxidative stress and inflammation are important pathogenic mediators in diabetes-related organ damage. Accumulating evidence suggests that immunodeficiency in diabetes is associated with diabetes-induced spleen damage. Sleeve gastrectomy (SG) has been proved to improve diabetes and its multiple associated complications. However, the ameliorative role of SG against spleen damage in diabetes has not been investigated. Animal model of diabetic obese rats induced by high-fat diet (HFD) combined with streptozotocin (STZ) was treated with sham operation, caloric restriction, and SG. Metabolic parameters were measured, and the morphological and histopathological changes, status of oxidative stress, and levels of inflammatory factors were evaluated. SG reduced body weight and improved glucose tolerance and insulin sensitivity in diabetic obese rats. SG significantly reversed splenic atrophy and alleviated abnormalities of white and red pulp. Additionally, SG also reversed the increased splenocyte apoptosis (P< 0.001). Meanwhile, indicators of oxidative stress including reactive oxygen species (ROS), nitric oxide (NO), malondialdehyde (MDA), and protein carbonylation were reduced, and the activity and expression of antioxidant enzymes including SOD and CAT were improved after SG. The mRNA expression of inflammatory factors in SG groups such as TNF-α (P< 0.001), IL-6 (P< 0.001), MCP-1 (P< 0.01), and ICAM-1 (P < 0.001) was also significantly reduced. SG ameliorates diabetes-related splenic injury by restoring the balance between oxidative stress process and antioxidant defense systems as well as reducing inflammation in the spleen. These findings indicate that SG is an appropriate therapeutic strategy for diabetes-related spleen damage.

Diabetic Conditions Confer Metabolic and Structural Modifications to Tissue-Engineered Skeletal Muscle.

Skeletal muscle is a tissue that is directly involved in the progression and persistence of type 2 diabetes (T2D), a disease that is becoming increasingly common. Gaining better insight into the mechanisms that are affecting skeletal muscle dysfunction in the context of T2D has the potential to lead to novel treatments for a large number of patients. Through its ability to emulate skeletal muscle architecture while also incorporating aspects of disease, tissue-engineered skeletal muscle (TE-SkM) has the potential to provide a means for rapid high-throughput discovery of therapies to treat skeletal muscle dysfunction, to include that which occurs with T2D. Muscle precursor cells isolated from lean or obese male Zucker diabetic fatty rats were used to generate TE-SkM constructs. Some constructs were treated with adipogenic induction media to accentuate the presence of adipocytes that is a characteristic feature of T2D skeletal muscle. The maturity (compaction and creatine kinase activity), mechanical integrity (Young's modulus), organization (myotube orientation), and metabolic capacity (insulin-stimulated glucose uptake) were all reduced by diabetes. Treating constructs with adipogenic induction media increased the quantity of lipid within the diabetic TE-SkM constructs, and caused changes in construct compaction, cell orientation, and insulin-stimulated glucose uptake in both lean and diabetic samples. Collectively, the findings herein suggest that the recapitulation of structural and metabolic aspects of T2D can be accomplished by engineering skeletal muscle in vitro.

Meliorative effects of Pergamum harmala seed extract on obese diabetic rats

Objective: To explore the potential antidiabetic activity of methanolic extract of Harmal seeds in obese-diabetic rats. Design: Randomized controlled experimental study. Animals: Forty male Sprague Dawley rats. Procedures: The P. harmala seeds methanolic extract was prepared and orally administered at two doses of 150 and 250 mg/kg to two groups of streptozotocin-induced diabetic rats. Two additional control groups were used as healthy control and obese-diabetic control groups. Animals were euthanized after 8 weeks of experimental period, blood and tissue samples were collected. Liver tissue samples were used to determine antioxidant and oxidative stress markers; while those from adipose tissue were used for estimation of PPAR gamma expression. Results: Supplementation of P. harmala methanolic extract with both doses (150 and 250 mg/kg) to diabetic rats (G3 and G4) significantly reversed the observed alterations in the levels of blood glucose, cholesterol, triglyceride, LDL, malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) (P &lt;0.05). . In addition, the downregulation of PPAR gamma expression in diabetic rats (G2) was also restored in rats (G3 and G4) supplemented with P.harmala methanolic extract. Conclusion and clinical relevance: Our finding revealed that Harmal seed extract has a potent antidiabetic activity in streptozotocin-induced diabetic rats that can be used as a dietary supplement by diabetic patients.

Ameliorative effects of Pergamum harmala seed extract on obese diabetic rats

Ameliorative effects of Pergamum harmala seed extract on obese diabetic rats

Effects of Chitosan Oligosaccharide on Plasma and Hepatic Lipid Metabolism and Liver Histomorphology in Normal Sprague-Dawley Rats.

Chitosan oligosaccharide is known to ameliorate hypercholesterolemia and diabetes. However, some studies found that chitosan oligosaccharide might induce mild to moderate hepatic damage in high-fat (HF) diet-induced obese rats or diabetic rats. Chitosan oligosaccharide can be as a dietary supplement, functional food, or drug. Its possible toxic effects to normal subjects need to be clarified. This study is designed to investigate the effects of chitosan oligosaccharide on plasma and hepatic lipid metabolism and liver histomorphology in normal Sprague-Dawley rats. Diets supplemented with 5% chitosan oligosaccharide have been found to induce liver damage in HF diet-fed rats. We therefore selected 5% chitosan oligosaccharide as an experimental object. Rats were divided into: a normal control diet group and a normal control diet +5% chitosan oligosaccharide group. The experimental period was 12 weeks. The results showed that supplementation of 5% chitosan oligosaccharide did not significantly change the body weight, food intake, liver/adipose tissue weights, plasma lipids, hepatic lipids, plasma levels of AST, ALT, and TNF-α/IL-6, hepatic lipid peroxidation and anti-oxidative enzyme activities, fecal lipids, and liver histomorphology in normal rats. These findings suggest that supplementation of 5% chitosan oligosaccharide for 12 weeks may not induce lipid metabolism disorder and liver toxicity in normal rats.

New Benzofuran N-Acylhydrazone Reduces Cardiovascular Dysfunction in Obese Rats by Blocking TNF-Alpha Synthesis.

IntroductionDiabetic obese patients are susceptible to the development of cardiovascular disease, including hypertension and cardiac dysfunction culminating in diabetic cardiomyopathy (DC), which represents a life-threatening health problem with increased rates of morbidity and mortality. The aim of the study is to characterize the effects of a new benzofuran N-acylhydrazone compound, LASSBio-2090, on metabolic and cardiovascular alterations in Zucker diabetic fatty (ZDF) rats presenting DC.MethodsMale non-diabetic lean Zucker rats (ZL) and ZDF rats treated with vehicle (dimethylsulfoxide) or LASSBio-2090 were used in this study. Metabolic parameters, cardiovascular function, left ventricle histology and inflammatory protein expression were analyzed in the experimental groups.ResultsLASSBio-2090 administration in ZDF rats reduced glucose levels to 85.0 ± 1.7 mg/dL (p < 0.05). LASSBio-2090 also lowered the cholesterol and triglyceride levels from 177.8 ± 31.2 to 104.8 ± 5.3 mg/dL and from 123.0 ± 11.4 to 90.9 ± 4.8 mg/dL, respectively, in obese diabetic rats (p < 0.05). LASSBio-2090 normalized plasma insulin, insulin sensitivity and endothelial function in aortas from diabetic animals (p < 0.05). It also enhanced systolic and diastolic left-ventricular function and reverted myocardial remodeling by blocking the threefold elevation of TNF-α levels in hearts from ZDF rats.ConclusionLASSBio-2090 alleviates metabolic disturbance and cardiomyopathy in an obese and diabetic rat model, thus representing a novel strategy for the treatment of cardiovascular complications in obesity-associated type 2 diabetes mellitus.

Modulation of metabolic alterations of obese diabetic rats upon treatment with Salacca zalacca fruits extract using 1H NMR-based metabolomics

Fruit of salak (Salacca zalacca) is traditionally used and commercialized as an antidiabetic agent. However, the scientific evidence to prove this traditional use is lacking. This research was aimed to evaluate the metabolic changes of obese-diabetic (OBDC) rats treated with S. zalacca fruit extract using proton-nuclear magnetic resonance (1H NMR)-based metabolomics approach. This research presents the first report on the in vitro antidiabetic effect of S. zalacca fruits extract using this approach. The obtained results indicated that the administration of 400 mg/kg bw of 60% ethanolic S. zalacca extract for 6 weeks significantly decreased the blood glucose level and normalized the blood lipid profile of the OBDC rats. The potential biomarkers in urine were 2-oxoglutarate, alanine, leucine, succinate 3-hydroxybutyrate, taurine, betaine, allantoin, acetate, dimethylamine, creatine, creatinine, glucose, phenyl-acetylglycine, and hippurate. Based on the data obtained, the 60% ethanolic extract could not fully improved the metabolic complications of diabetic rats. The extract of S. zalacca fruit was able to decrease the ketones bodies as 3-hydroxybutyrate and acetoacetate. It also improved energy metabolism, involving glucose, acetate, lactate, 2-hydroxybutyrate, 2-oxoglutarate, citrate, and succinate. Moreover, it decreased metabolites from gut microflora, including choline. This extract had significant effect on amino acid metabolism, metabolites from gut microflora, bile acid metabolism and creatine. The result can further support the traditional claims of S. zalacca fruits in management of diabetes. This finding might be valuable in understanding the molecular mechanism and pharmacological properties of this medicinal plant for managing diabetes mellitus.

THE ROLE OF VISFATIN AND CYTOGLOBIN IN OBESE DIABETIC RATS: THE MODULATORY EFFECTS OF RASPBERRY KETONE

Introduction: Clinical and epidemiological studies suggest that patients who are overweight or obese are more at risk in developing glucose intolerance (G/I) and insulin resistance (I/R) leading to type 2 diabetes (T2DM) and cardiovascular disease. Aim of work: Assess the dynamic contribution of visfatin in the development of obesity and/or diabetes and demonstrate their possible molecular mechanism(s) from side and from another side, modulate role of Raspberry ketone (RK) as weight management supplement and illustrate their possible molecular mechanism(s). Materials and Methods: Eighty adult rats were divided into eight groups (10 rats for each group, G); G1: Normal Control Group (Normal diet); G2: Diabetic Control Group (received streptozotocin 35 mg/kg); G3: Obese Control Group (received high fat diet, HFD); G4: Obese Diabetic Control Group, G5: Raspberry ketone Control Group (received 500 mg/kg), G6: Diabetic rats treated with Raspberry ketone; G7: Obese rats treated with Raspberry ketone and G8: Obese Diabetic rats treated with Raspberry ketone to assess the study’s aims, their effect was determined on body weight, OGTT, glucose homeostasis (glucose, insulin, HOMA-IR), oxidative stress markers, cytoglobin, visfatin and liver histopathology. Results: RK caused weight loss, corrected the disturbed glucose and insulin homeostasis, Furthermore, RK increased hepatic content of glutathione (GSH), while decreased hepatic content of malonaldialdehyde (MDA). RK also up regulated hepatic protein expression of cytoglobin, while down regulated hepatic mRNA expression of visfatin. Conclusion: This study assessed the involvement of visfatin and cytoglobin in obese diabetic rats and modulated the role of RK through the efficient rebalance of glucose homeostasis, I/R, the redox status and liver histopathology.

611-P: Splenic Stimulation with Focused Ultrasound Aids in Wound Healing

Wound care in at risk populations is a growing problem. The cost of care of these non-healing wounds is projected to be in the billions with the number of people affected being above 6.5 million and increasing as the population ages. There is significant mortality related with non-healing wounds with 5-year rates being higher than many cancers such as prostate or breast. Chronic inflammation, a comorbidity of type 2 diabetes, when left unchecked may result in non-healing wounds. This study explores the use of non-invasive focused ultrasound (FUS) targeted to the spleen to aid in healing of full thickness excision skin wounds in Obese Zucker Diabetic (ZDF) or Zucker Diabetic Sprague Dawley (ZDSD) rats. Splenic stimulation with FUS has been shown to decrease TNF-α 60 minutes post stimulation in both whole blood and the spleen of animals injected with LPS. By decreasing systemic proinflammatory cytokines, wounds may progress to better outcomes. In the current study, FUS was targeted to the spleen daily while wounds were healing (16 days). Hyperglycemic (fed glucose &amp;gt;250 mg/dL) ZDF stimulated with FUS were predicted (by linear regression) to heal 5 days faster than shams (17.1 ±0.8 days vs. 22.3±1.6 days respectively). Glucose levels remained similar throughout the study. The same FUS conditions were applied to prediabetic ZDSD (fed glucose &amp;lt; 195 mg/dL). FUS stimulated rats were predicted to heal 2 days faster than shams (20 ±1.2 vs. 22.3±1.1 respectively). Disclosure C.A. Morton: None. V.E. Cotero-Lefevre: None. C. Puleo: Employee; Self; General Electric. J. Ashe: Employee; Self; General Electric.

Effects of a Red Orange and Lemon Extract in Obese Diabetic Zucker Rats: Role of Nicotinamide Adenine Dinucleotide Phosphate Oxidase.

Diabetic nephropathy (DN) is the primary cause of end-stage renal disease, worldwide, and oxidative stress has been recognized as a key factor in the pathogenesis and progression of DN. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has the most important contribution to reactive oxygen species generation during the development of DN. Bioactive compound use has emerged as a potential approach to reduce chronic renal failure. Therefore, a red orange and lemon extract (RLE) rich in anthocyanins was chosen in our study, to reduce the toxic renal effects during the development of DN in Zucker diabetic fatty rat (ZDF). RLE effects were examined daily for 24 weeks, through gavage, in ZDF rats treated with RLE (90 mg/kg). At the end of the experiment, ZDF rats treated with RLE showed a reduction of the diabetes-associated up-regulation of both NOX4 and the p47-phox and p22-phox subunits, and restored the BAX/BCL-2 ratio respect to ZDF rats. Furthermore, RLE was able to reduce the oxidative DNA damage measured in urine samples in ZDF rats. This study showed that RLE could prevent the renal damage induced by DN through its capacity to inhibit NOX4 and apoptosis mechanisms.

Role of linagliptin in preventing the pathological progression of hepatic fibrosis in high fat diet and streptozotocin-induced diabetic obese rats

Liver fibrosis is a common complication of diabetes mellitus, with a major global public health concern. Linagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4), is classically used to treat type 2 diabetes mellitus and improves insulin resistance. Additional potential influences of linagliptin on liver fibrosis are still unclear. The present study was undertaken to investigate the therapeutic credit of linagliptin in hepatic fibrosis induced by a high-fat diet (HFD) and streptozotocin (STZ) in rats. Moreover, the mechanisms underline its anti-fibrotic effect were explored. To induce liver fibrosis with T2DM; male Sprague-Dawley albino rats were fed on a high-fat high-sucrose diet for 28 days then exposed to a single dose of STZ (30 mg/kg, IP). After two days of STZ injection, a diabetes confirmation test was done and all diabetic rats were constantly fed on HFD for thirty days with or without treatment with linagliptin (6 mg/kg). Hepatotoxicity markers, lipid profile screening, insulin signaling, inflammatory cytokines (TNF-α, IL-6, NF-κB p65), fibrosis markers (Collagen, α-SMA, TGF-β1) and histopathological studies including hematoxylin and eosin (H&E) as well Masson's trichrome stains were performed. In our preliminary study, linagliptin at a dose of 6 mg/kg was chosen as the optimum anti-diabetic dose in rats challenged with STZ. Linagliptin significantly improved insulin sensitivity and lipid profile and reduced inflammatory mediators, and collagen depositions in rats with liver fibrosis and T2DM. In conclusion, above and beyond its anti-diabetic effect, this study introduced linagliptin as a promising option for preventing the pathological progression of liver fibrosis associated with T2DM.

Sleeve Gastrectomy Attenuates Diabetic Nephropathy by Upregulating Nephrin Expressions in Diabetic Obese Rats.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and sleeve gastrectomy (SG) is considered to be an effective strategy to improve pre-existing DN. However, the mechanism remains unknown. Animal model of DN was induced by high-fat diet (HFD) and streptozotocin (STZ). SG or sham surgery was performed and rats were sacrificed at 4, 8, and 12weeks after surgery. The basic parameters (blood glucose, body weight, kidney weight), indicators of renal function including serum creatinine (Scr), blood urea nitrogen (BUN), urine microalbumin, urine creatinine (Ucr), microalbumin creatinine ratio (UACR), ultrastructural changes of glomerulus, and the expression of nephrin gene and protein in glomerular podocytes were compared among groups. Blood glucose and body weight of SG rats were significantly lower than those of the sham-operated rats, and renal function of SG groups were also significantly improved within the postoperative period of 12weeks. The results of periodic acid-Schiff staining (PAS) and transmission electron microscopy (TEM) showed that glomerular hypertrophy and accumulation of extracellular matrix proteins were significantly alleviated after SG, and the thickness of basement membrane and the fusion or effacement of foot processes were also significantly improved. The mRNA and protein expression of nephrin in SG groups was significantly higher than that in the sham group. These results suggest that SG attenuates DN by upregulating the expression of nephrin and improving the ultrastructure of glomerular filtration membrane. This study indicates that SG can be used as an available therapeutic intervention for DN.

Treatment of insulin resistance in obesity-associated type 2 diabetes mellitus through adiponectin gene therapy.

Global rise in obesity-associated type 2 diabetes mellitus (T2DM) has led to a major healthcare crisis. Development of efficient treatments to treat the underlying chronic inflammation in obesity-associated T2DM, is an unmet medical need. To this end, we have developed a plasmid adiponectin (pADN) based nanomedicine for the treatment of insulin resistance in type 2 diabetes mellitus. Adiponectin is a potent anti-inflammatory/anti-diabetic adipokine, which is downregulated in obesity. In this study, nanomicelles comprising chitosan conjugated to oleic acid and adipose homing peptide (AHP) were developed to deliver pADN to adipocytes. Cationic chitosan-oleic-AHP micelles were 112nm in size, encapsulated 93% of pADN and protected gene cargo from DNase I mediated enzymatic degradation. In vitro, the nanomicellar formulation significantly increased adiponectin production compared to free plasmid as well as standard transfecting agent FuGENE®HD. Single dose subcutaneous administration of pADN-chitosan-oleic-AHP to obese-diabetic rats, resulted in improved insulin sensitivity for up to 6weeks, which matched the glucose disposal ability of healthy rats. Serum adiponectin level in pADN-chitosan-oleic-AHP treated rats was comparable to healthy rats for up to 3weeks post treatment. Overall, the results indicate that pADN-chitosan-oleic-AHP based therapy is a promising treatment approach for obesity-associated T2DM.

Transplantation of Endothelial Progenitor Cells in Obese Diabetic Rats Following Myocardial Infarction: Role of Thymosin Beta-4.

Endothelial progenitor cells (EPCs) are bone-marrow derived cells that are critical in the maintenance of endothelial wall integrity and protection of ischemic myocardium through the formation of new blood vessels (vasculogenesis) or proliferation of pre-existing vasculature (angiogenesis). Diabetes mellitus (DM) and the metabolic syndrome are commonly associated with ischemic heart disease through its pathological effects on the endothelium and consequent endothelial dysfunction. Thymosin-β4 (Tβ4) which expressed in the embryonic heart is critical in epicardial and coronary artery formation. In this study, we explored the effects of Tβ4 treatment on diabetic EPCs in vitro and intramyocardial injection of Tβ4-treated and non-Tβ4 treated EPCs following acute myocardial infarction (MI) of diabetic rats in vivo. It was found that 10 ng/mL Tβ4 increased migration, tubule formation, and angiogenic factor secretion of diabetic EPCs in vitro. In vivo, although implantation of Tβ4 treated diabetic EPCs significantly increased capillary density and attracted more c-Kit positive progenitor cells into the infarcted hearts as compared with implantation of non-Tβ4 treated diabetic EPCs, the significantly improved left ventricular ejection fraction was only found in the rats which received non-Tβ4 treated EPCs. The data suggests that a low dose Tβ4 increases diabetic EPC migration, tubule formation, and angiogenic factor secretion. However, it did not improve the effects of EPCs on left ventricular pump function in diabetic rats with MI.

Effect of Interval and Continued Exercises with Crocin on Bax/Bcl-2 in Diabetic Obese Rats

Objective: Diabetes is a metabolic disease which is linked to increased physical disabilities and muscle tissue damage. The aim of this study was to investigate the effect of interval and continued exercises with crocin on Bax/Bcl-2 ratio in diabetic obese rats. Materials and Methods: In this clinical trial study, 56 adult diabetic rats (high-fat diet and venous injection of streptozotocin) were selected and randomly assigned to groups (1), intense interval exercises (2), low intensity exercise (3), intense interval exercise with crocin consumption, (4) Low intensity exercise with crocin consumption, (5) Crocin consumption, (6) sham and (7) control were divided. Intense interval and low intensity exercise groups lasted for 8 weeks, three sessions per week, with intensity of 80 to 85 and 50 to 55 percent of maximum treadmill running, and crocin consumption groups for 8 weeks per day, mg / kg 25 crocin were taken peritoneal. To analyze the research hypotheses, Kolmogorov- Smirnov tests, independent T- tests and two-way multi-variable analysis of variance were used along with Benferron's comparison method. It should be noted that the significance level in all measurements was considered to be P -value≤ 0.05. Results: Results showed that exercise ( P -value: 0.12) and crocin ( P value: 0.10) consumption had no significant effect on Bax/Bcl-2 gene expression in diabetic rats. Also interaction of exercise and crocin consumption on Bax/Bcl-2 was not significant ( P -value: 0.12). Conclusion: It appears that exercise and crocin consumption have not interaction effect on improvement of Bax / Bcl-2 ratio in diabetic rats.

Protective effect of adropin against high fat diet-induced obese diabetic wistar rats via nuclear factor erythroid 2-related factor 2 pathway

Introduction: Liver steatosis (fatty liver) is frequently found during the conditions such as diabetes and obesity. The current experimental study was executed the effect of adropin against high fat diet (HFD)-induced obese diabetic Wistar rats via nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Materials and Methods: Wistar rats were randomly divided into six groups and divided as follows: normal, HFD control, HFD + adropin (2.5, 5 and 10 mg/kg), and HFD + Glibenclamide (2.5 mg/kg), respectively. Lipid and carbohydrate metabolism, hepatic parameters, antioxidant, and proinflammatory cytokines were estimated at the end of the experimental study. Nrf2 transcription and nuclear level were also estimated. In vitro adropin diminished the accumulation of lipid droplets in dose-dependent manner and no effect was observed on the lipolysis. Type II diabetic rats fed with HFD exhibited a marked reduction in hepatic extraction faction and hepatic steatosis after the adropin and glibenclamide treatment. Results: Adropin significantly (P

Roux-en-Y Gastric Bypass in Obese Diabetic Rats Promotes Autophagy to Improve Lipid Metabolism through mTOR/p70S6K Signaling Pathway.

Purpose To investigate the effects of Roux-en-Y gastric bypass (RYGB) surgery on markers of liver mitochondrial dynamics and find new therapeutic basis on obese type 2 diabetes mellitus (T2DM) patients. Materials and Methods. Thirty-two rats were divided into nondiabetic group, diabetic group, sham group, and RYGB group. The Dual-energy X-ray absorptiometry (DEXA) was used to detect short-term curriculum vitae for rat body component and fat and lean mass. Hepatic lipid content and triglyceride levels were detected by Oil Red O staining. Western blotting was used to examine autophagy and mammalian target of rapamycin/P70S6 kinase (mTOR/p70S6K) pathway-related proteins. The carbon dioxide production from the oxidation of [14C] oleate was measured. Plasma glucose was measured by glucose oxidase assay. The insulin and C-peptide were detected. Triacylglyceride (TG) and free fat acid (FFA) in plasma were determined by enzymatic colorimetric assays. Results RYGB improved metabolic parameters and enhanced plasma GLP-1 level, ameliorated the lipopexia, and increased insulin sensitivity in the liver; RYGB promoted the hepatic autophagy and inhibited the mTOR/p70S6K signaling pathway. GLP-1 reduced fat load and increased fatty acid β-oxidation by activated autophagy to regulate the hepatic lipid pathway through mTOR/p70S6K signaling pathway. Conclusions RYGB may reduce liver lipid toxicity and improve insulin sensitivity through activating the hepatic fat hydrolysis pathway and inhibiting the liver fat synthesis pathway. However, the transport pathway of liver fat does not play a key role.

The Effect of Subdiaphragmatic Vagotomy on Lipid Profile and Insulin Resistance in Diabetic Obese Rats

The aim of the study was to assess of the effect of subdiaphragmatic vagotomy on lipid profile and insulin resistance in diabetic obese rat model. Fifty Male Albino rats were divided into 5 groups. Subdiaphragmatic vagotomy and sham operations were applied on diabetic obese rat model induced by high fat diet for 5 weeks and low dose of streptozotocin (30mg/kg). Serum samples were collected for confirmation of hyperlipidemia and lee obesity index was measured. At the end of the experiment, oral glucose tolerance test, lee obesity index, lipid profile, fasting insulinemia, fasting glucose, insulin resistance (HOMA-IR) and histopathology of pancreases were assessed. Results revealed that Subdiaphragmatic vagotomy significantly improved hyperlipidemia as it normalized plasma triglyceride level, decreased plasma cholesterol level and increased plasma high density lipoprotein level in diabetic and non-diabetic obese vagotomized rats. Vagotomy significantly decreased lee obesity index and perigonadal fat pads weight, decreased fasting insulinemia, decreased HOMA-IR and improved glucose tolerance in diabetic and non-diabetic obese vagotomized rats. These results were confirmed by regression of degenerative changes and restoration of the size of pancreatic islets of Langerhans. In non-diabetic obese vagotomized group, the results of 120 minutes of oral glucose tolerance test and HOMA-IR were close to normal expected values. However, the same parameters were still away from normal expected values although normal histopathological results of pancreases, in diabetic obese vagotomized group. In Conclusion, subdiaphragmatic vagotomy has a promising role in treating obesity. Nevertheless, its role in treating diabetes needs further long-term studies to be approved.