High-fat Diet Control Group Research Articles

Dual targeting of Nur77 and AMPKα by isoalantolactone inhibits adipogenesis in vitro and decreases body fat mass in vivo.

Suppression of adipogenesis has been considered as a potential target for the prevention and treatment of obesity and associated metabolic disorders, and the nuclear receptor 4A1 (NR4A1/Nur77) and AMPKα are known to play important roles during early and intermediate stages of adipogenesis. Therefore, we hypothesized that dual targeting Nur77 and AMPKα would show strong inhibitory effect on adipogenesis. We screened a herbal medicine-based small molecule library to identify novel natural compounds dual targeting Nur77 and AMPKα, and the antiadipogenic effects and mechanisms of action of a "hit" compound were studied in 3T3-L1 cells. In vivo antiobesity effects of the compound were also investigated in high-fat diet (HFD)-induced obese mice. We identified isoalantolactone (ISO) as a new NR4A1 inactivator that also activates AMPKα in 3T3-L1 cells. ISO, as expected, inhibited adipogenic differentiation of 3T3-L1 preadipocytes, accompanied by reduced mitotic clonal expansion (MCE) which occurs in the early stage of adipogenesis and decreased expression of genes required for MCE and cell cycle markers including cyclin A, cyclin D1. Furthermore, ISO reduced body weight gain and fat mass (epididymal, subcutaneous, perirenal, and inguinal white adipose tissues) in the high-fat diet-fed C57BL/6 N mice. Serum levels of triglycerides, aspartate transaminase, and alanine transaminase and hepatic steatosis were also significantly improved in the ISO-treated group compared to the high-fat diet control group. These results suggest that ISO dual targeting Nur77 and AMPKα during adipogenesis represents a novel class of mechanism-based antiadipogenic agents for treatment of obesity and associated metabolic disorders, including hyperlipidemia and fatty liver.

Anti-hypercholesterolemic effect of Zingiber montanum extract

Background: Hypercholesterolemia, high cholesterol levels in the blood, can contribute to many forms of disease, most notably cardiovascular disease. Anti-hypercholesterolemic agents generally used for those conditions have several side effects for patients. Zingiber montanum, known locally as “bangle”, belongs to the family Zingiberaceae and is a potential plants for alternative anti-hypercholesterolemic agents. This plant, from East Kalimantan, is used in traditional medicine for health problems caused by high cholesterol levels. The aim of this research was to find alternatives to anti-hypercholesterolemic agents, especially from natural sources. Methods: This study was an experimental study using 30 Wistar male white rats. Subjects were randomly divided into 6 groups (n=5): (1) normal control group; (2) high fat diet control group; (3) high fat diet with simvastatin; (4-6) high fat diet with Zingiber montanum extracts 100, 200, and 400 mg/kg. After 4 weeks of treatment, blood was collected from all groups, and plasma concentrations of triglycerides, total cholesterol, high density lipoproteins (HDL), and low density lipoproteins (LDL) were measured. Results: The results showed significant differences in total cholesterol (p=0.000), LDL (p=0.000) and triglycerides (p=0.001) in the high-fat diet group with Z. montanum extract, as compared to the high-fat diet control. Meanwhile, there were no significant differences in HDL levels (p=0.830) between the high-fat diet group and other groups. The results also showed significant differences in total cholesterol and LDLs for rats treated with Z. montanum extract, 100 mg/kg (p=0.000), 200 mg/kg (p=0.000), and 400 mg/kg (p=0.000) compared to the high-fat diet group. The result of Z. montanum 400 mg/kg also showed a significant reduction, not only for total cholesterol and LDLs, but also for triglycerides (p=0.030). Conclusion: It could be concluded that Z. montanum extracts have the potency to be further developed as a new natural source of the anti-hypercholesterolemic agents.

Docosahexaenoic acid-flurbiprofen combination ameliorates metaflammation in rats fed on high-carbohydrate high-fat diet

ObjectivePotential benefits of combining docosahexaenoic acid (DHA), an omega-3 fatty acid with flurbiprofen (Flu), a non-steroidal anti-inflammatory drug in ameliorating obesity remain to be elucidated. This study aimed to investigate the possible protective effects of DHA and Flu, either alone or in combination, against obesity-induced metaflammation and to clarify the underlying molecular mechanisms. MethodsSeventy-five male Wistar rats were divided into five groups: normal diet (ND) group, high-carbohydrate high-fat diet (HCHFD) control group, DHA group (HCHFD + 200 mg/kg DHA), Flu group (HCHFD + 10 mg/kg Flu), and DHA + Flu group (HCHFD + DHA + Flu). Treatments were administered orally daily for 8 consecutive weeks, parallel with the start of diets. ResultsPlasma levels of glucose, insulin, and TGs were significantly reduced in DHA, Flu, and DHA + Flu treated groups, while HDL-C concentrations were significantly elevated in the same groups, compared to HCHFD control group. Only Flu and DHA + Flu groups showed a significant decrease in plasma levels of leptin, TC, and LDL-C, relative to HCHFD control group. Concentrations of phosphorylated adenosine monophosphate-activated protein kinase (pAMPK) and resolvin D1 (RvD1) in epididymal adipose tissue (EAT) were significantly increased in the three treated groups, compared with HCHFD control group. Expression of AMPK-α1 subunit in EAT was significantly increased, whereas expression of nuclear factor kappa B (NF-κB) was significantly decreased in EAT of the three treated groups, relative to HCHFD control group. ConclusionsDocosahexaenoic acid-flurbiprofen combination showed an ameliorative effect on obesity-associated metaflammation and its consequences in rats.

Antihyperglycemic and Antihyperlipidemic Effects of Low-molecular-weight Carrageenan in Rats.

This study investigated the antihyperglycemic and antihyperlipidemic effects of low-molecular-weight carrageenan (LC) on rats fed a high-fat diet. Wistar rats were divided into five groups: normal control group (NC), high-fat diet control group (HC), carrageenan-treated control group (CC), 1% LC group (1% LC), and 3% LC-groups (3% LC). Body weight, food intake, fecal weight, blood glucose, and serum lipid levels were measured. After 30 days, body weight significantly decreased in the LC-treated groups than in the HC group. Moreover, in the LC-treated groups, postprandial blood glucose, total cholesterol, triglyceride, and low-density lipoprotein cholesterol (LDL-C) levels decreased, whereas high-density lipoprotein cholesterol (HDL-C) levels increased. From this study, our data suggest that LC has antihyperglycemic and hypolipidemic effects when compared to carrageenan, likely related to its increased absorption due to its lower molecular weight.

Antiobesity Effect of Tricin, a Methylated Cereal Flavone, in High-Fat-Diet-Induced Obese Mice.

The antiobesity potential of tricin, a methylated cereal flavonoid, was examined using a high-fat-diet-induced obese mice model. The body weight ( P < 0.01) and body fat mass ( P < 0.05) were significantly decreased in the high-dose tricin supplementation group (TH: 200 mg/kg diet) in comparison to the high fat diet control group (CON) after a 12-week feeding trial. The serum (60.9 ± 2.09 mg/dL) and hepatic triglyceride levels (45.3 ± 4.42 nmol/mg protein) in the TH group were significantly decreased in comparison to the CON group (78.3 ± 5.09 mg/dL, 76.3 ± 8.10 nmol/mg protein), respectively. This antiobesity effect was attributed to a decrease in the expression of lipogenic markers crucial for fat synthesis in the liver (fatty acid synthase, stearoyl-CoA desaturase 1, elongation of long-chain fatty acids family member 6, glycerol-3-phosphate acyltransferase, and diglyceride acyltransferase) and suppressed expression of transcription factors associated with adipocyte differentiation (peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α). These lipid-lowering effects are mediated by the activation of adenosine 5'-monophosphate-activated protein kinase.

Pharmacological Action of a Pregnane Glycoside, Russelioside B, in Dietary Obese Rats: Impact on Weight Gain and Energy Expenditure.

Background and purpose: Russelioside B (RB) is a pregnane glycoside obtained from Caralluma quadrangula; a herb with antidiabetic, anti-inflammatory, and antihyperlipidemic activities. The present experiment tested the possible role of RB in controlling weight gain in rats fed on high fat (HF) diet.Methods: RB was separated from the n-butanol fraction of the crude methanolic extract by chromatographic separation on a Si gel column according to the procedures described previously. The experiment of the biological assessment of RB used 32 male Wistar rats (4 groups, n = 8). Group 1 rats were fed with a palatable normal diet. Group 2, 3, and 4 were fed on HF diet for 16 weeks. Group 2 served as the HF diet control group while Group 3 and 4 received daily oral doses of RB (25 and 50 mg/kg) during the last four weeks. Animals’ parameters like weight gain, fasting level of blood sugar, serum lipids, and serum liver enzyme activities were measured. Liver or adipose tissue weight was divided by the rat’s body weight and multiplied by 100 to obtain the liver or adipose tissue index, respectively. Adipose tissues were processed for histopathological examination, measurement of mRNA expression of visfatin, leptin, adiponectin, uncoupling protein-1 (UCP-1), and carnitine palmitoyl transferase-1 (CPT-1). Furthermore, serum levels of insulin, interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), leptin, resistin, and adiponectin were assessed using ELISA kits.Results: Rats fed with the HF diet exhibited significant body weight gain, abnormal liver function, disturbed lipid profile, and greater serum level of pro-inflammatory cytokines in addition to greater insulin resistance, adipose tissue and liver indices. Further, rats fed with the HF diet displayed upregulations in the expression of visfatin and leptin with downregulations in the expression of adiponectin, UCP-1, and CPT-1 compared to normal rats. Interestingly, RB (25 or 50 mg/kg) favorably modulated the measured parameters.Conclusion: Data from this study documented the beneficial role of RB in diminishing weight gain, improving the inflammatory perturbations and energy expenditure in HF diet fed rats. Therefore, RB might be a promising candidate for obesity.

PBI-4547 Improves Glucose Metabolism and Insulin Resistance, and Reduces Liver Damage in a High-Fat Diet Mouse Model of Obesity and Metabolic Syndrome

Introduction and Aims: Obesity and its resulting metabolic disturbances are major health threats and are the main cause of a host of diseases, including nonalcoholic fatty liver disease (NAFLD). PBI-4547 is a novel first-in-class orally active antidiabetic compound which displays pleiotropic activities and has been shown to reduce NASH, diabetes, and renal fibrosis in different animal models. The aim of this study was to investigate the effects of PBI-4547 in a mouse model of high-fat diet-induced obesity and metabolic syndrome. Methods: C57BL/6 mice were fed with either a standard or a high-fat diet (HFD, Harlan, TD.06414) for 14 weeks. These mice were divided in three groups [normal chow, HFD + vehicle, and HFD + PBI-4547 (10 mg/kg, oral once a day)] and treated for an additional 6 weeks. Blood glucose, serum insulin level, serum triglyceride and adiponectin, liver histology, as well as liver and white adipose tissue (WAT) pro-inflammatory/fibrotic gene expression were examined. Results: In an oral glucose tolerance test, PBI-4547 increased glucose metabolism compared to the HFD control group. Insulin resistance (measured by HOMA-IR) and β cell function (HOMA1-β) were improved by PBI-4547. Serum triglyceride level was significantly reduced by PBI-4547 while adiponectin in serum was significantly increased. Histological analysis showed a significant reduction of hepatic steatosis and ballooning by PBI-4547. To further characterize the activity of PBI-4547, quantitative RT-PCR analysis of pro-fibrotic markers was performed, demonstrating that PBI-4547 reduced CTGF and MMP2 gene expression in the liver as well as CTGF, MCP-1, MMP2 and collagen type I gene expression in the WAT. Conclusions: Taken together, these results suggest that PBI-4547 offers the potential as a novel therapy for nonalcoholic fatty liver disease, obesity and associated metabolic syndrome. Disclosure M. Leduc: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. B. Grouix: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. M. Tremblay: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. L. Gervais: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. F. Sarra-Bournet: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. A. Felton: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. J. Simard: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. F.A. Leblond: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc. P. Laurin: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc.. Board Member; Self; Prometic Life Sciences Inc. L. Gagnon: Employee; Self; Prometic Biosciences Inc.. Stock/Shareholder; Self; Prometic Life Sciences Inc..

Astragaloside IV Prevents Obesity-Associated Hypertension by Improving Pro-Inflammatory Reaction and Leptin Resistance.

Low-grade pro-inflammatory state and leptin resistance are important underlying mechanisms that contribute to obesity-associated hypertension. We tested the hypothesis that Astragaloside IV (As IV), known to counteract obesity and hypertension, could prevent obesity-associated hypertension by inhibiting pro-inflammatory reaction and leptin resistance. High-fat diet (HFD) induced obese rats were randomly assigned to three groups: the HFD control group (HF con group), As IV group, and the As IV + α-bungaratoxin (α-BGT) group (As IV+α-BGT group). As IV (20 mg·Kg−1·d−1) was administrated to rats for 6 weeks via daily oral gavage. Body weight and blood pressure were continuously measured, and NE levels in the plasma and renal cortex was evaluated to reflect the sympathetic activity. The expressions of leptin receptor (LepRb) mRNA, phosphorylated signal transducer and activator of transcription-3 (p-STAT3), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), suppressor of cytokine signaling 3 (SOCS3) mRNA, and protein-tyrosine phosphatase 1B (PTP1B) mRNA, pro-opiomelanocortin (POMC) mRNA and neuropeptide Y (NPY) mRNA were measured by Western blot or qRT-PCR to evaluate the hypothalamic leptin sensitivity. Additionally, we measured the protein or mRNA levels of α7nAChR, inhibitor of nuclear factor κB kinase subunit β/ nuclear factor κB (IKKβ/NF-KB) and pro-inflammatory cytokines (IL-1β and TNF-α) in hypothalamus and adipose tissue to reflect the anti-inflammatory effects of As IV through upregulating expression of α7nAChR. We found that As IV prevented body weight gain and adipose accumulation, and also improved metabolic disorders in HFD rats. Furthermore, As IV decreased BP and HR, as well as NE levels in blood and renal tissue. In the hypothalamus, As IV alleviated leptin resistance as evidenced by the increased p-STAT3, LepRb mRNA and POMC mRNA, and decreased p-PI3K, SOCS3 mRNA, and PTP1B mRNA. The effects of As IV on leptin sensitivity were related in part to the up-regulated α7nAchR and suppressed IKKβ/NF-KB signaling and pro-inflammatory cytokines in the hypothalamus and adipose tissue, since co-administration of α7nAChR selective antagonist α-BGT could weaken the improved effect of As IV on central leptin resistance. Our study suggested that As IV could efficiently prevent obesity-associated hypertension through inhibiting inflammatory reaction and improving leptin resistance; furthermore, these effects of As IV was partly related to the increased α7nAchR expression.

High-fat diet aggravates postoperative cognitive dysfunction in aged mice

BackgroundSilent Information Regulator 1 (Sirt1) and apoptosis play key roles in postoperative cognitive dysfunction (POCD). Consuming a high-fat diet (HFD), a prevalent type of diet in modern society, has been increasingly recognized as contributing to neurodegenerative diseases. Although Sirt1 and apoptosis are significant responders to HFD in the brain, little is known regarding the functional correlations between HFD and POCD.MethodsThirty-two aged C57BL/6 male mice were randomly divided into 2 groups: an ad libitum (AL) group (fed a regular diet) and high-fat diet (HF) group (fed a high-fat diet). After 8 weeks, the animals were divided into four sub-groups: an ad libitum control (ALC) group, ad libitum surgery (ALS) group, high-fat diet control (HFC) group, and high-fat diet surgery (HFS) group. The ALS and HFS groups were exposed to 3% sevoflurane in 33% oxygen for 3 h and were subsequently subjected to exploratory surgery to establish the POCD model. The ALC and HFC groups were treated with 33% oxygen for 3 h without surgery. After 48 h, the learning and memory abilities of mice in each group were tested using the Morris water maze (MWM). The expression levels of Sirt1, Bcl-2, Bax and caspase-3 cleaved were detected by western blot.ResultsThe MWM and western blotting results showed that the learning and memory abilities were decreased in the HFC group compared with the ALC group. The learning and memory abilities and the expression of Sirt1 in the hippocampus in the HFS group were significantly decreased compared with the other groups. A significant decrease in Sirt1 expression was also observed in the HFC group compared with the ALS group. The level of Bcl-2 was lower in the HFS group than in the HFC and ALC groups. The expression levels of caspase-3 cleaved and Bax increased in the HFS group compared with the HFC group. Moreover, the expression of caspase-3 cleaved was higher in the HFC group than in the ALS group.ConclusionHFD can aggravate POCD in aged C57BL/6 mice, an effect that may be related to the inhibition expression of Sirt1 and the promotion of neuronal apoptosis.

Disheveled 2 around the implant at an early stage of hyperlipidemic rats

This study aims to investigate the expression of disheveled 2 (Dvl2) around the implant of hyperlipidemic rats at an early stage after the implantation. A total of 24 Wistar rats were divided equally into the experimental group fed with high-fat diet group and control group fed with a normal diet. After 8 weeks, the serum lipid levels were detected, and rats received implants in the femur metaphysis. Rats were sacrificed at 1, 3, and 5 days after implantation, and the bones around implants were obtained. Methylene blue-acid fuchsin staining was performed to observe the implant-bone interface. Real-time polymerase chain reaction was performed on runt-related transcription factor 2 (Runx2), cathepsin K (CatK), and Dvl2. Dvl2 Western blot or immunoprecipitation, phosphorylation, and ubiquitination were also conducted. In the experimental group, less osteoblasts, lower expression of Runx2 and Dvl2, and lower Dvl2 phosphorylation (P<0.05) than those of the control group were observed; furthermore, the CatK expression and Dvl2 ubiquitination were higher than those in the control group (P<0.05). Hyperlipidemia may suppress bone remodeling around the implant at an early stage by Dvl2 down-regulation, phosphorylation, and up-regulated ubiquitination.

Maraviroc improves hepatic triglyceride content but not inflammation in a murine nonalcoholic fatty liver disease model induced by a chronic exposure to high-fat diet

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the general population. Its severity ranges from simple steatosis to cirrhosis. C-C chemokine ligand type 5 or RANTES (Regulated upon Activation, Normal T-cell Expressed, and Secreted) plays an important role in the progression of hepatic inflammation and fibrosis. Our objective was to examine the preventive and therapeutic effects of maraviroc (MVC), a C-C chemokine receptor 5 antagonist, on liver pathology in an NAFLD mouse model. A total of 60 male C57BL/6 mice were randomly assigned to 1 of 4 groups: (1) high-fat diet (HFD) group or control group, (2) preventive group (HFD group plus MVC in drinking water since the beginning of the study), (3) early-therapeutic group (HFD group plus MVC in drinking starting at week 24 of the study), and (4) late-therapeutic group (HFD group plus MVC in drinking water starting at week 36 of the study). All mice were sacrificed at week 48. The hepatic triglyceride concentration in the HFD group was significantly higher than that in the groups treated with MVC at any time. Gene expression associated with lipogenesis (diacylglycerol acyltransferase 2 and proliferator-activated receptor-γ), insulin resistance (insulin receptor substrate-2), and β-oxidation (carnitine palmitoyltransferase 1A and acyl-CoA oxidase) was significantly reduced in all the groups treated with MVC. In summary, the beneficial effect of MVC on hepatic steatosis is maintained throughout the study.

Protective Effect of Meretrix meretrix Oligopeptides on High-Fat-Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice.

The present study investigated the effects of MMO (Meretrix meretrix oligopeptides) on mice fed a high-fat diet. Mice were fed either a normal control diet (NC) or a high-fat diet (HFD) without or with MMO (50 mg/kg or 250 mg/kg) for four weeks. Levels of ALT, AST, liver tissue GSH-Px, and SOD activities, MDA levels were measured using commercially available kits; HE staining was performed to analyze pathologic changes of the liver; a TEM assay was performed to measure the ultrastructural alterations of the mitochondria, and Western blotting was performed to detect the expression of gene proteins related to lipid metabolism, inflammation, and liver apoptosis. After six weeks, body weight, ALT, AST, and MDA levels were significantly increased, and GSH-Px levels and SOD activities were significantly decreased in the HFD control group compared with the NC group. Consumption of the HFD compared with the NC caused fatty liver abnormal mitochondria with loss of cristae, intramitochondrial granules, and a swollen and rarefied matrix. Administration of MMO significantly decreased body weight gain, and ALT, AST, and MDA levels; increased SOD activity and GSH-Px levels; alleviated fatty liver steatosis; decreased the early apoptosis population; downregulated SREBP-1c, Bax, Caspase-9, Caspase-3, TNF-α, and NF-κB protein levels; and upregulated PPAR-α, Bcl-2, and AMPK-α, compared with the HFD control group. MMO exhibited protective effects in mice with NAFLD by regulating the NF-κB anti-inflammation signaling pathways to inhibit inflammation, regulate AMPK-α, PPAR-α and SREBP-1c to improve lipid metabolism disorder, and regulate Bcl-2/Bax anti-apoptosis signaling pathways to prevent liver cell apoptosis. These results suggest that dietary supplementation with MMO ameliorates high-fat-diet-induced NAFLD.

Effect of atorvastatin on the gut microbiota of high fat diet-induced hypercholesterolemic rats

The aim of the present study was to investigate alterations in gut microbiota associated with hypercholesterolemia and treatment with atorvastatin, a commonly prescribed cholesterol-lowering drug. In this study, seven experimental groups of rats were developed based on diets [high-fat diet (HFD) and normal chow diet (NCD)] and various doses of atorvastatin in HFD and NCD groups. 16S rRNA amplicon sequencing was used to analyze the gut microbiota. Atorvastatin significantly reduced the cholesterol level in treated rats. Bacterial diversity was decreased in the drug-treated NCD group compared to the NCD control, but atorvastatin-treated HFD groups showed a relative increase in biodiversity compared to HFD control group. Atorvastatin promoted the relative abundance of Proteobacteria and reduced the abundance of Firmicutes in drug-treated HFD groups. Among the dominant taxa in the drug-treated HFD groups, Oscillospira, Parabacteroides, Ruminococcus, unclassified CF231, YRC22 (Paraprevotellaceae), and SMB53 (Clostridiaceae) showed reversion in population distribution toward NCD group relative to HFD group. Drug-treated HFD and NCD groups both showed an increased relative abundance of Helicobacter. Overall, bacterial community composition was altered, and diversity of gut microbiota increased with atorvastatin treatment in HFD group. Reversion in relative abundance of specific dominant taxa was observed with drug treatment to HFD rats.

Effects and mechanism of hypoxia exposure on related genes in brown fat tissue of obese mice based on mRNA expression profile microarray

This study intended to screen differentially expressed genes and pathways in Brown Adipose Tissue (BAT) of obese mice after the intervention of hypoxia by mRNA expression profile microarray, exploring the mechanism of hypoxia activated BAT. Thirty C57BL/6J male mice were divided into the normal diet control group (N, n=8), high-fat diet control group (OB, n=8) and high-fat diet hypoxia group (H, n=8). Group H was intervened by hypoxia exposure in the oxygen concentration of 11.2% of the normal oxygen and hypoxia for 8 h/d, 6 d/w of 4 weeks. Blood lipid and blood glucose were detected after intervention; RNA microarray scan and bioinformation analysis were done of BAT from scapula. Genes significantly (P ≤ 0.05) regulated more than 1.5 fold were chosen to do Gene Ontology and enrichment analysis by KOBAS 2.0, and confirmation of genes participating in key biological process (BP) and pathway was done by real time qPCR. After intervention, the body weight and blood lipid and glucose levels in group H were significantly lower than those of group OB. Comparing with group N, 802 genes were significantly up-regulated and 1 175genes were down-regulated. The BP of these genes mainly concerned with glucose and lipid metabolic process and inflammatory reaction. Comparing with group OB, 297 genes were significantly up-regulated and 228 genes were down-regulated. These genes participated in glucose and lipid metabolic process, lipid transport, muscle system process and cardiovascular system development. The pathways of regulating BAT by hypoxia exposure mainly concentrated on the HIF-1, PI3K-AKT, FoxO and ErbB signaling pathways. A series of genes and pathways in BAT could be adjusted by hypoxia exposure, so that hypoxia could improve the activity of BAT, promoting obese organism to lose weight.

Improvement of Diet-induced Obesity by Ingestion of Mushroom Chitosan Prepared from Flammulina velutipes.

The anti-obesity effects of mushroom chitosan prepared from Flammulina velutipes were investigated using an animal model with diet-induced obesity. In this study, 5-week-old imprinting control region (ICR) mice were divided into six groups of 10 mice each and fed different diets based on the MF powdered diet (standard diet) for 6 weeks: standard diet control group, high-fat diet control group (induced dietary obesity) consisting of the standard diet and 20% lard, and mushroom chitosan groups consisting of the high-fat diet with mushroom chitosan added at 100, 500, 1,000, and 2,000 mg/kg body weight. On the final day of the experiment, mean body weight was 39.1 g in the high-fat control group and 36.3 g in the 2,000 mg/kg mushroom chitosan group, compared to 35.8 g in the standard diet control group. In the mushroom chitosan groups, a dose-dependent suppression of weight gain and marked improvements in serum triglycerides, total cholesterol, LDL-cholesterol, and HDL-cholesterol were found. The mushroom chitosan groups showed fewer and smaller fat deposits in liver cells than the high-fat diet control group, and liver weight was significantly reduced. Glutamic oxaloacetic transaminase (GOT) and glutamate pyruvic transaminase (GPT), which are indices of the hepatic function, all showed dose-dependent improvement with mushroom chitosan administration. These results suggested that mushroom chitosan acts to suppress enlargement of the liver from fat deposition resulting from a high-fat diet and to restore hepatic function. The lipid content of feces showed a marked increase correlated with the mushroom chitosan dose. These findings suggest the potential use of mushroom chitosan as a functional food ingredient that contributes to the prevention or improvement of dietary obesity by inhibiting digestion and absorption of fats in the digestive tract and simultaneously promotes lipolysis in adipocytes.

Preparation, characterization and hypolipidaemic activity of Astragalus membranaceus polysaccharide

The dried root of Astragalus membranaceus (A. membranaceus) is an important traditional Chinese herbal medicine. The polysaccharide from A. membranaceus (AMP) exhibits numerous biological activities. This study aimed to investigate the hypolipidaemic effect of AMP. Male Sprague–Dawley rats were divided into four groups: one group was treated with a high-fat diet (control group), and three groups were treated with high-fat diet containing 50, 100 and 150 mg/kg of AMP. AMP treatment decreased the levels of plasma triacylglycerol (TG), plasma total cholesterol (TC), plasma low-density lipoprotein cholesterol, liver weight and liver TC and TG levels. Moreover, AMP treatment increased the levels of faecal fat, cholesterol and plasma high-density lipoprotein cholesterol of rats compared with the control group. Therefore, AMP possesses a potent hypolipidaemic activity and may be used for hyperlipidaemia treatment.

Gypenosides Reduced the Risk of Overweight and Insulin Resistance in C57BL/6J Mice through Modulating Adipose Thermogenesis and Gut Microbiota.

This study investigated whether and how gypenosides from jiaogulan tea at 100 and 300 mg/kg/day levels could reduce the development of overweight and insulin resistance in C57 BL/6J mice fed a high-fat diet in 12 weeks. The 300 mg/kg/day gypenosides supplement significantly reduced final body weight, plasma total cholesterol, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) index by 19.9%, 40%, and 36%, respectively, compared with the high-fat diet control group. Gypenosides also increased brown adipocyte tissue activity and white adipose tissue browning. The expression of genes involved in mitochondrial activity and fatty acid β-oxidation were also increased in both brown and white adipocyte tissues. In addition, gypenosides at 100 and 300 mg/kg/day levels decreased the ratio of Firmicutes to Bacteroidetes by 20% and 58.6%, respectively, and increased Akkermansia muciniphila abundance in the gut microbiota.

Oral delivery of quercetin in oil-in-water nanoemulsion: In vitro characterization and in vivo anti-obesity efficacy in mice

We sought to design an effective oral delivery system for quercetin (QCN) to enhance its solubility and bioavailability and thus improve its anti-obesity effects. QCN-loaded oil-in-water nanoemulsion was prepared by an aqueous phase titration method. The optimized formulation had a mean particle size of 19.3±0.17nm with a zeta potential of −0.34±0.13mV. In vitro permeabilities of QCN from the nanoemulsion through an artificial intestinal membrane and Caco-2 cell monolayer were 188- and 3.37-fold higher than those of an aqueous dispersion of QCN, respectively, and the resulting in vivo oral bioavailability was 33.51-fold greater than that of free QCN. Furthermore, high-fat-diet (HFD)-treated mice given daily the oral QCN-loaded nanoemulsion had a maximal reduced weight gain of 23.5% compared with the HFD control group. These findings suggest that a QCN-loaded nanoemulsion may be a promising oral therapy for the treatment of obesity.

Isoproterenol exacerbates hyperglycemia and modulates chromium distribution in mice fed with a high fat diet

Background and purposeIsoproterenol (ISO), a nonselective β-adrenoceptor agonist for treating bradycardia and asthma, has been proposed to raise blood glucose level. Little is known regarding the relationship between ISO treatment, the induced chromium (Cr) redistribution, and changes in glucose metabolism. We aimed to characterize the effects of a single dose of ISO on glucose homeostasis and Cr level changes in an obesity mouse model. MethodsMice (C57BL6/j strain) were first fed for a continuous period of 12 weeks with either a high fat diet (HFD), to develop an obesity animal model, or a standard diet (SD), to develop a lean animal model as controls. These groups were each separated into two subgroups to receive either a single dose of ISO or saline (control). We measured in vivo their metabolic parameters, fasting glucose level, area under the curve (AUC) for glucose level time profile, insulin level time profile, insulin sensitivity index, and chromium distribution. ResultsAfter a single dose of ISO, the SD-fed mice had slightly higher blood glucose levels compared with the SD controls, when the level was measured 30 and 60min after injection. By contrast, the ISO-treated HFD-fed mice had significantly higher blood glucose levels and AUC during the entire 120min following one administration compared with the HFD control group. Additionally, they had a substantially lower HOMA-IR index, whereas insulin levels remained unchanged. The Cr level in their bones and liver was decreased, and loss of Cr through urinary excretion was elevated. ConclusionThe results demonstrated that ISO exacerbated hyperglycemic syndrome in the obesity animal model. ISO induced a net negative Cr balance as a result of increased urinary excretion, leading to Cr mobilization that was not desirable to overcome the hyperglycemia.

The mTORC2/PKC pathway sustains compensatory insulin secretion of pancreatic β cells in response to metabolic stress

BackgroundCompensation of the pancreatic β cell functional mass in response to metabolic stress is key to the pathogenesis of Type 2 Diabetes. The mTORC2 pathway governs fuel metabolism and β cell functional mass. It is unknown whether mTORC2 is required for regulating metabolic stress-induced β cell compensation. MethodsWe challenged four-week-old β-cell-specific Rictor (a key component of mTORC2)-knockout mice with a high fat diet (HFD) for 4weeks and measured metabolic and pancreatic morphological parameters. We performed ex vivo experiments to analyse β cell insulin secretion and electrophysiology characteristics. Adenoviral-mediated overexpression and lentiviral-ShRNA-mediated knocking down proteins were applied in Min6 cells and cultured primary mouse islets. ResultsβRicKO mice showed a significant glucose intolerance and a reduced plasma insulin level and an unchanged level β cell mass versus the control mice under HFD. A HFD or palmitate treatment enhanced both glucose-induced insulin secretion (GIIS) and the PMA (phorbol 12-myristate 13-acetate)-induced insulin secretion in the control islets but not in the βRicKO islets. The KO β cells showed similar glucose-induced Ca2+ influx but lower membrane capacitance increments versus the control cells. The enhanced mTORC2/PKC proteins levels in the control HFD group were ablated by Rictor deletion. Replenishing PKCα by overexpression of PKCα-T638D restored the defective GIIS in βRicKO islets. ConclusionsThe mTORC2/Rictor pathway modulates β cell compensatory GIIS under nutrient overload mediated by its phosphorylation of PKCα. General significanceThis study suggests that the mTORC2/PKC pathway in β cells is involved in the pathogenesis of T2D.