高脂饮食诱导肥胖大鼠的胰岛素敏感性与FFAs变化的关系

目的 :观察正常大鼠在高脂饮食诱导下形成肥胖后 ,胰岛素敏感性及其FFAs的变化。方法 :9周龄健康雄性Wistar大鼠16只 ,随机分为正常饲养组 (NC,n=8)和高脂饲养组 (HF,n=8)。喂养10周 ,比较两组大鼠体重、HOMA -IR以及FFAs等的变化。结果 :经10周高脂喂养 ,HF组与NC组比较 ,体重和内脏脂肪组织显著增加 (HF组大鼠体重较NC组增加了11 4% ,P<0 05) ;HF组大鼠内脏脂肪组织较NC组增加了20 7% ,P<0 01) ,并出现胰岛素抵抗 (HOMA -IR :HF组8 88±4 25vs3 92±2 26 ,P<0 05) ,空腹FFAs水平显著上升 ,较NC组增加了80 8% (P<0 05) ,但两组空腹血糖差异无显著性 ,HF组 :(7 89±1 46)mmol/LvsNC组 (8 70±1 59)mmol/L,P>0 05。结论 :高脂饮食可诱导大鼠肥胖伴胰岛素抵抗 ,其胰岛素抵抗的形成可能与FFAs水平的升高有关     

阿托伐他汀对高脂饮食大鼠非酒精性脂肪性肝炎的影响

目的观察阿托伐他汀对高脂饮食大鼠非酒精性脂肪性肝炎(NASH)的影响。方法将23只SD大鼠随机分为三组:正常对照组(NC组,8只)、高脂饲养模型组(HF组,7只)和高脂饲养+阿托伐他汀组(HF+AT组,8只)。观察大鼠血清及肝脏各指标的变化,RT-PCR分别检测肝组织核转录因子κB(NF-κB)、肿瘤坏死因子α(TNF-α)及过氧化物酶体增生物激活受体γ(PPARγ)mRNA表达。结果与HF组相比,HF+AT组大鼠血清相关指标明显改善,肝组织脂肪变性及炎症活动得以减轻,肝脏NF-κB及TNF-αmRNA表达降低,PPARγmRNA表达增加(P<0.05或P<0.01)。结论阿托伐他汀能减轻高脂诱导的模型大鼠NASH。     

高脂诱导性肥胖大鼠的胰岛素敏感性与TNF-αFFAs水平

目的观察正常大鼠在高脂饮食诱导下形成肥胖后的胰岛素敏感性及其TNF-α、FFAs的变化.方法9周龄健康雄性Wistar大鼠16只,随机分为正常饲养组(NC,n=8)和高脂饲养组(HF,n=8).喂养10周,比较两组大鼠体重、胰岛素抵抗指数(HOMA-IR)、以及TNF-α、FFAs等的变化.结果经10周高脂喂养,HF组与NC组比较,体重和内脏脂肪组织显著增加(HF组大鼠体重较NC组增加了11.4%,P＜0.05;HF组大鼠内脏脂肪组织较NC组增加了20.7%,P＜0.01),并出现胰岛素抵抗(HOMA-IRHF组为8.88±4.25,NC组为3.92±2.26,P＜0.05),空腹FFAs和TNF-α水平显著上升，较NC组分别增加了80.8%(P＜0.05)和58.4%(P＜0.05),但两组空腹血糖差异无显著性(HF组为7.89±1.46mmol/L,NC组为8.70±1.59mmol/L,P＞0.05).结论高脂饮食可诱导大鼠肥胖伴胰岛素抵抗,其胰岛素抵抗的形成可能与TNFα、FFAs水平的升高有关.     

高脂诱导性肥胖大鼠的胰岛素敏感性与TNF-α及FFAs水平

目的观察正常大鼠在高脂饮食诱导下形成肥胖后的胰岛素敏感性及其TNF-α、FFAs的变化。方法9周龄健康雄性Wistar大鼠16只,随机分为正常饲养组(NC熏n=8)和高脂饲养组(HF熏n=8)。喂养10周,比较两组大鼠体重、胰岛素抵抗指数(HOMA-IR)、以及TNF-α、FFAs等的变化。结果经10周高脂喂养,HF组与NC组比较,体重和内脏脂肪组织显著增加(HF组大鼠体重较NC组增加了11.4%,P<0.05;HF组大鼠内脏脂肪组织较NC组增加了20.7%,P<0.01),并出现胰岛素抵抗(HOMA-IR:HF组为8.88±4.25,NC组为3.92±2.26熏P<0.05),空腹FFAs和TNF-α水平显著上升,较NC组分别增加了80.8%(P<0.05)和58.4%(P<0.05),但两组空腹血糖差异无显著性(HF组为7.89±1.46mmol/L,NC组为8.70±1.59mmol/L熏P>0.05)。结论高脂饮食可诱导大鼠肥胖伴胰岛素抵抗,其胰岛素抵抗的形成可能与TNFα、FFAs水平的升高有关。     

Crocetin improves the insulin resistance induced by high-fat diet in rats

BACKGROUND AND PURPOSE: The amelioration of insulin resistance by treatment with crocetin is closely related to the hypolipidaemic effect. The present study is designed to clarify the insulin-sensitizing mechanism of crocetin by elucidating the mechanism of regulation of lipid metabolism by crocetin. EXPERIMENTAL APPROACH: Rats given a high-fat diet were treated with crocetin for 6 weeks before hyperinsulinaemic-euglycaemic clamp. 14C-palmitate was used as tracer to track the fate of non-esterified fatty acids or as substrate to measure beta-oxidation rate. Triglyceride clearance in plasma and lipoprotein lipase activity in tissues were tested. Content of lipids in plasma and tissues was determined. Real-time PCR was used to assay the level of mRNA from genes involved in non-esterified fatty acid and triglyceride uptake and oxidation. KEY RESULTS: Crocetin prevented high-fat-diet induced insulin resistance (increased clamp glucose infusion rate), raised hepatic non-esterified fatty acid uptake and oxidation, accelerated triglyceride clearance in plasma, enhanced lipoprotein lipase activity in liver, and reduced the accumulation of detrimental lipids (DAG and long-chain acyl CoA) in liver and muscle. Genes involved in hepatic lipid metabolism which are regulated by peroxisome proliferator-activated receptor-alpha, were modulated to accelerate lipid uptake and oxidation. CONCLUSIONS AND IMPLICATIONS: Through regulating genes involved in lipid metabolism, crocetin accelerated hepatic uptake and oxidation of non-esterified fatty acid and triglyceride, and reduced lipid availability to muscle, thus decreasing lipid accumulation in muscle and liver, and consequently improving sensitivity to insulin.     

苦瓜提取物对高脂饲料诱导肥胖大鼠的减肥作用

目的研究苦瓜提取物对高脂膳食诱导肥胖大鼠的减肥作用和可能机制。方法高脂饲料喂养制备肥胖大鼠模型,然后随机分为空白对照组、模型对照组和苦瓜提取物36 g.kg-1治疗组,分别灌胃给予质量分数为0.5%的羧甲基纤维素钠和苦瓜提取物,给药周期为6周,实验过程中每周记录体质量,最后一周测定摄食量,实验结束后检测体内脂肪含量,检测血清高密度脂蛋白(highdensity lipoprotein,HDL)、低密度脂蛋白(low density lipoprotein,LDL)、谷草转氨酶(aspartate ami-no transaminase,AST)和谷丙转氨酶(alanine amino transferase,ALT)水平以及肝脏脂肪病变。结果苦瓜提取物能够在不影响大鼠摄食量的基础上抑制肥胖大鼠的体质量增长速度,降低其体质量和附睾下脂肪量,升高血清中HDL水平,降低血清中AST水平,抑制肝细胞脂肪变性;而对Lee's指数、肠系膜和肾周脂肪量、血清中LDL和ALT水平无明显影响。结论苦瓜提取物具有一定减肥和保肝作用,该作用可能与升高血清HDL水平和降低血清AST水平以及抑制肝细胞脂肪变性有关。     

高脂所致脂肪肝动物模型建立的动态研究

目的建立大鼠高脂血症及非酒精性脂肪肝模型,观察肝脏脂变程度和时间的动态关系,以找到合适的高脂血症和脂肪肝模型造模时间。方法采用W istar大鼠50只,饲喂高脂饲料,分别检测2~6 wk大鼠血清TG、TC、HDL、LDL、AST、ALT水平,根据肝脏病理切片分析肝脏脂变情况。结果在饲喂高脂饲料2 wk后,大鼠出现高血脂症状并伴有轻度的脂肪肝,随后的几周血脂水平保持稳定上升,肝系数持续增大,肝脏组织细胞脂变程度随造模时间的延长逐渐加重,3~4 wk为中度,5~6 wk为重度,第6周时伴有脂肪纤维化症状。结论经过高脂饲料的喂养,6 wk内可形成不同脂变程度的脂肪肝病理模型,可用于相关药理实验。     

Low molecular weight chitosan inhibits obesity induced by feeding a high-fat diet long-term in mice

Three low molecular weight chitosans (molecular weight: 21, 46 and 130 kDa) obtained by enzymatic hydrolysis of a high molecular weight chitosan (average molecular weight: 650 kDa) had low viscosity and were water-soluble. The effects of these water-soluble chitosans on pancreatic lipase (in-vitro) and the elevation of plasma triacylglycerol concentration after the oral lipid tolerance test were examined in mice. The water-soluble 46-kDa chitosan was the most effective at inhibiting pancreatic lipase activity (in-vitro) and plasma triacylglycerol elevation after the oral lipid tolerance test. Based on this result, the effects of the 46-kDa chitosan on increases in bodyweight, various white adipose tissue weights, and plasma and liver lipids were examined in mice fed a high-fat diet for 20 weeks. Water-soluble 46-kDa chitosan (300 mg kg(-1), twice daily) prevented increases in bodyweight, various white adipose tissue weights and liver lipids (cholesterol and triacylglycerol) in mice fed a high-fat diet, and further increased the faecal bile acid and fat. The results suggest that the lipid-lowering effects of the 46-kDa chitosan may be mediated by increases in faecal fat and/or bile acid excretion resulting from the binding of bile acids, and by a decrease in the absorption of dietary lipids (triacylglycerol and cholesterol) from the small intestine as a result of the inhibition of pancreatic lipase activity. Water-soluble 46-kDa chitosan (100 and 300 mg kg(-1), twice daily) did not cause liver damage with the elevation of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, or kidney damage with the elevation of blood nitrogen urea. It was concluded that water-soluble 46-kDa chitosan is a safe functional food.     

Cepharanthine action in preventing obesity and hyperlipidemia in rats on a high-fat high sucrose diet

BackgroundIt was demonstrated that cepharanthine (CEP), derived from Stephania cepharantha hayata, is a potent inhibitor of the ABCC10 transmembrane protein. It is approved to be a natural product or remedy. The present study focuses on investigating whether cepharanthine effectively reduces hyperlipidemia and obesity in an experimental hyperlipidemic rat model.MethodFour groups of Wistar rats were assigned randomly to the following groups: a high-fat high sucrose diet (HFHS), normal-fat diet (NFD), HFHS plus cepraranthine (10 mg/kg) (HFHS-C), and a HFHS diet with atorvastatin (HFHS-A). The responses of rats were observed on the basis of serum and hepatic biochemical parameters, food intake, and body weight after CEP treatment, and assessing the histopathological modifications by the optical microscope in the liver and its cells.ResultsSignificant improvement in the serum total cholesterol (TC), serum triglycerides (TG), and serum low-density lipoprotein (LDL) levels were observed following CEP treatment. We have also observed significant improvement in the structure of liver tissue and reduced-fat droplets in the cytoplasm. Moreover, CEP had a significant effect in preventing the gain in body weight of animals, and food intake was not significantly affected.ConclusionOur research results revealed that CEP significantly improved dyslipidemia and prevented the accumulation of fatty deposits in the rats' liver tissue fed an HFHS diet. In addition, CEP exerted an anti-obesity effect.     

Ameliorative effect of berberine on endothelial dysfunction in diabetic rats induced by high-fat diet and streptozotocin

Berberine can improve insulin resistance, lower blood glucose, and regulate lipid metabolism disorders which cause endothelial dysfunction, leading to vascular complications of type 2 diabetes mellitus. The aim of the present study was to investigate the effects of berberine on endothelial dysfunction of aortas in type 2 diabetes mellitus rats and its mechanism. Wistar rats were randomly divided into four groups: diabetic rats, control rats, diabetic rats treated with berberine (100 mg/kg), and control rats treated with berberine. The serum fasting blood glucose, insulin, total cholesterol, triglyceride and nitric oxide (NO) levels were tested. Acetylcholine-induced endothelium-dependent relaxation and sodium nitroprusside induced endothelium-independent relaxation were measured in aortas for estimating endothelial function. The expression of endothelial nitric oxide synthase (eNOS) mRNA was measured by RT-PCR, and the protein expressions of eNOS and NADPH oxidase (NOX4) were analyzed by western blot. The results showed that berberine significantly decreased fasting blood glucose, and triglyceride levels in diabetic rats. Berberine also improved endothelium-dependent vasorelaxation impaired in aorta. The expressions of eNOS mRNA and protein were significantly increased, while NOX4 protein expression was decreased in aortas from diabetic rats with berberine treatment. Moreover, serum NO levels were elevated after berberine treatment. In conclusion, berberine restores diabetic endothelial dysfunction through enhanced NO bioavailability by up-regulating eNOS expression and down-regulating expression of NADPH oxidase.     

高脂膳食诱导肥胖大鼠的瘦素水平分析

目的:研究高脂膳食诱导对肥胖大鼠瘦素水平的影响.方法:将50只雄性Wistar大鼠随机分为高脂膳食组和正常对照组,分别用高脂饲料和基础饲料喂养8周,观察体质量变化,第八周末测定并比较血脂和血清瘦紊水平.结果:本次研究高脂膳食诱导肥胖大鼠的体质量、血清总胆固醇和瘦素水平均显著高于正常对照组.结论:高脂膳食诱导的肥胖大鼠易产生瘦素抵抗,并伴有一定程度的血脂代谢紊乱.     

Pharmacokinetics of verapamil in diabetic rats induced by combination of high-fat diet and streptozotocin injection

1. The aim of this study was to investigate effects of type 2 diabetes on the pharmacokinetics of verapamil after intravenous administration.

2. Diabetes mellitus (DM) rats were induced by combination of high-fat diet (HFD) and streptozotocin. Plasma concentrations of verapamil in DM rats, rats fed with HFD, and control (CON) rats were measured after intravenous administration of 1?mg/kg verapamil and corresponding pharmacokinetic parameters were estimated. Area under the plasma concentration in DM rats was significantly smaller than that in CON rats.

3. In vitro microsomal study showed that intrinsic clearance of verapamil in DM rats was significantly higher than those in CON rats. Compared to CON rats, higher intrinsic clearance was also observed in HFD rats. Western blot results demonstrated higher levels of CYP3A2 in DM and HFD rats, which was in line to activity of CYP3A.

4. All the results gave a conclusion that diabetes may enhance metabolism of verapamil in rat, and the enhancement may partly result from induction of CYP3A.

     

Pharmacokinetics of verapamil in diabetic rats induced by combination of high-fat diet and streptozotocin injection

The aim of this study was to investigate effects of type 2 diabetes on the pharmacokinetics of verapamil after intravenous administration. Diabetes mellitus (DM) rats were induced by combination of high-fat diet (HFD) and streptozotocin. Plasma concentrations of verapamil in DM rats, rats fed with HFD, and control (CON) rats were measured after intravenous administration of 1?mg/kg verapamil and corresponding pharmacokinetic parameters were estimated. Area under the plasma concentration in DM rats was significantly smaller than that in CON rats. In vitro microsomal study showed that intrinsic clearance of verapamil in DM rats was significantly higher than those in CON rats. Compared to CON rats, higher intrinsic clearance was also observed in HFD rats. Western blot results demonstrated higher levels of CYP3A2 in DM and HFD rats, which was in line to activity of CYP3A. All the results gave a conclusion that diabetes may enhance metabolism of verapamil in rat, and the enhancement may partly result from induction of CYP3A.     

Wild ginseng prevents the onset of high-fat diet induced hyperglycemia and obesity in icr mice

Ginseng is a shade-loving perennial herb that is cultivated mainly in Korea, Japan, and China. The ginseng root has been used as a tonic remedy, and its antidiabetic activity has been demonstrated as early as 1920s. Although wild ginseng was anecdotally thought to be superior to cultivated ginseng as far as pharmacological properties were concerned, there have been no prior reports on the antidiabetic effect of wild ginseng. In this study, we investigated the preventative anti-diabetic and anti-obese effects of wild ginseng ethanol extract (WGEE). In the preventive experiment, WGEE co-administered with a high fat diet significantly inhibited body weight gain, fasting blood glucose, triglyceride, and free fatty acid levels in a dose dependent manner. WGEE-treated mice at doses of 250 and 500 mg/kg improved the insulin resistance index by 55% and 61% compared to the high fat diet (HFD) control, respectively. Diameters of white and brown adipocytes were also decreased by 62% and 46% in the WG500-treated group compared to those in HFD fed control mice. Taken together, WGEE has potential as a preventive agent for type 2 diabetes mellitus (and possibly obesity) and deserves clinical trial in the near future.     

肥胖对雄性大鼠成年期慢性应激诱导抑郁症的影响

目的通过高脂饲料诱发的SD大鼠肥胖模型,研究肥胖对抑郁症发病的影响。方法选取8周龄健康成年雄性SD大鼠38只（体质量200～250 g）,将其分为对照组（8只）、单纯抑郁症组（15只）和肥胖伴抑郁症组（15只）。对照组和单纯抑郁症组给予普通饲料,肥胖伴抑郁症组给予高脂饲料,连续喂养10周。通过喂养高脂饲料诱发大鼠肥胖;采用慢性不可预期性应激程序刺激大鼠建立抑郁症模型;运用糖水偏好测试、强迫游泳实验、开野实验测定大鼠抑郁状态,观察肥胖对抑郁症发病的影响。结果各组大鼠喂养5周后体质量均增加,喂养高脂饲料的肥胖伴抑郁症组大鼠体质量增加明显高于对照组和单纯抑郁症组;经不可预期性应激程序刺激后,单纯抑郁症组、肥胖伴抑郁症组大鼠均出现抑郁症状,且肥胖伴抑郁症组症状更明显。结论肥胖可能是诱发抑郁症的一个高风险因素。     

Beneficial effects by intake of Euphausiacea pacifica on high-fat diet-induced obesity

Obesity is a major health problem showing increased incidence in developed and developing countries. We examined the effect of Euphausia pacifica (E. pacifica) (Pacific Krill) on high-fat diet (HFD)-induced obesity in C57BL/6 mice. No significant differences were observed in average food intake between the HFD and HFD with E. pacifica group, or the low-fat diet (LFD) and LFD with E. pacifica group for 18 weeks. The increased ratio of body weight in the HFD containing E. pacifica group was significantly reduced, being 10% lower than that with HFD group in the 18th week (HFD, 298.6±18.8% vs. HFD with E. pacifica, 267.8±16.2%; p<0.05), while the ratio for the LFD containing E. pacifica group was reduced by 4% compared with LFD group (LFD, 244.2±11.6% vs. LFD with E. pacifica, 234.1±18.0%). There were no effects of E. pacifica on total cholesterol levels in serum and liver, whereas the supplement of E. pacifica tended to decrease triglyceride levels in the HFD groups. The leptin level in serum was significantly decreased in the HFD group (p<0.01) by E. pacifica. The adipocyte area (1926±1275 μm(2)) in the HFD containing E. pacifica group was significantly reduced by 20% (p<0.001) compared with the HFD group. These results suggested that E. pacifica supplementation in the diet is beneficial for the prevention of HFD-induced obesity.     

机械加载对高脂饮食诱导的肥胖和非酒精性脂肪肝的治疗作用

目的 探讨机械加载对高脂饮食诱导的肥胖和非酒精性脂肪肝的疗效。方法 选用6周龄的C57BL/6雌性小鼠30只,体质量约18 g,按随机数字表法分为正常对照组（NC组）、高脂饮食组（HF组）和高脂饮食机械加载治疗组（HF+L组）,每组10只,持续饮食诱导12周。高脂饮食6周后,HF+L组进行机械加载治疗6周。实验动物进行体成分分析,观测全身体脂含量的变化。收集肾周脂肪、子宫周脂肪、肠系膜脂肪、腹股沟脂肪和肝脏并称量湿质量。留取部分肝脏做组织形态学检测,油红O和HE染色分析观察肝脏的病理改变,部分肝脏用于Western blot检测内质网应激相关蛋白（eIF2α、p-eIF2α、ATF4）的表达。结果 与NC组相比,高脂饮食导致HF组体质量、体脂明显增加,机械加载治疗后,HF+L组体质量、体脂较HF组明显降低（P＜0.05）。肝脏组织学结果表明,高脂饮食导致一定程度的肝脏脂肪变性,通过治疗后,脂肪变性得到有效缓解（P＜0.05）。Western blot分析结果表明,高脂饮食导致小鼠肝脏eIF2α、p-eIF2α和ATF4蛋白表达升高,机械加载能够抑制肝脏p-eIF2α和ATF4蛋白的表达。结论 机械加载能够有效缓解高脂饮食导致的体质量、体脂增加及非酒精性脂肪肝,其治疗作用可能与肝脏内质网应激有关。     

白藜芦醇对高脂饮食诱导小鼠高脂血症的作用机制研究

目的 考察白藜芦醇对高脂血症小鼠的影响,并探讨其作用机制.方法 按体重将雄性C57BL/6J小鼠随机分为3组:正常组、模型组及实验组,每组10只.正常组正常饲养,模型组及实验组小鼠连续饲喂4周高脂饲料构建高血脂模型.建模后,实验组灌服白藜芦醇(400 mg·kg-1),模型组及空白组灌服等量生理盐水,每天1次,连续干预...     

Hypolipidemic and body fat-lowering effects of Fatclean in rats fed a high-fat diet

The body fat-lowering and hypolipidemic effects of a Fatclean formula were examined in Sprague–Dawley rats fed a high-fat diet. Animals were given a normal control (NC) diet or a 15% high-fat (HF) diet with or without Fatclean (5%, wt/wt) supplement for 6 weeks. Fatclean formula contained phenolic compounds (14.3 mg/g) and other functional compounds. Fatclean formula significantly lowered final body weights and visceral fat-pads weights, plasma total cholesterol (TC) and triglyceride (TG) concentrations, hepatic cholesterol and triglyceride levels, and hepatic hydroxyl-3-methylglutaryl-coenzyme A reductase (HMG-CoA) and acyl-coenzyme A:cholesterol acyltransferase (ACAT) activities compared to the HF group. Furthermore, adipocytic lipoprotein lipase (LPL) activity was also significantly elevated in the Fatclean group than in the HF group. The high-density lipoprotein–cholesterol/total-cholesterol (HDL–C/Total-C) ratio and atherogenic index (AI) were significantly improved in the Fatclean group than in the HF group. The accumulation of hepatic lipid droplets and the epididymal white adipocyte size were diminished in the Fatclean group than in the HF group. Accordingly, Fatclean seemed to be beneficial for the reduction of body weight and/or body fat and its hyperlipidemic property was highly active for enhancing the plasma lipids profile.