Fucoidan Prevents High‐Fat Diet‐Induced Obesity in Animals by Suppression of Fat Accumulation

This study examines the antiobesity effects of fucoidan in an animal model of diet‐induced obesity. Mice were fed a standard diet or high‐fat diet (HFD) for 5 weeks. After that, the mice were divided into four experimental groups, with 10 mice per group, including a standard diet group, HFD group, HFD containing 1% fucoidan (HFD + FUCO 1%) group and HFD containing 2% fucoidan (HFD + FUCO 2%) group. The fucoidan supplementation group had significantly decreased body‐weight gain, food efficiency ratio and relative liver and epididymal fat mass compared with the HFD group. The mice supplemented with fucoidan showed significantly reduced triglyceride, total cholesterol and low‐density lipoprotein levels in the plasma. Liver steatosis induced by the HFD improved in the fucoidan‐supplemented group. Furthermore, fucoidan affected the down‐regulation expression patterns of epididymal adipose tissue genes such as peroxisome proliferator‐activated receptor γ, adipose‐specific fatty acid binding protein and acetyl CoA carboxylase. Therefore, fucoidan may be considered for use in improving obesity. Copyright © 2013 John Wiley & Sons, Ltd.     

苦瓜乙醇提取物对肥胖大鼠糖代谢和内脏脂肪的影响

目的 研究苦瓜乙醇提取物对喂饲高脂饲料所致肥胖大鼠糖代谢和内脏脂肪量的影响.方法 高脂饲料饲养制备肥胖大鼠模型.肥胖大鼠随机分为模型组,苦瓜乙醇提取物低、中、高剂量(9、18、36 g/kg)组,左旋肉碱(600 mg/kg)阳性对照组,另设对照组(正常饲料饲养)和苦瓜乙醇提取物36 g/kg给药组.各组大鼠每天ig相应药物或等体积0.5％羧甲基纤维素钠溶液,每天记录摄食量,每周记录体质量.给药第6周进行糖耐量实验:给药7周后所有动物禁食18h,麻醉后腹主动脉采血,检测血清葡萄糖和胰岛素水平;分离附睾、肾周和肠系膜脂肪并称质量,附睾脂肪组织随后进行HE染色检测脂肪细胞病变.结果 苦瓜乙醇提取物36 g/kg能够明显降低肥胖大鼠体质量,抑制大鼠食物利用率,减少附睾、肾周和肠系膜白色脂肪量,降低空腹血糖浓度,抑制附睾脂肪细胞肥大;苦瓜乙醇提取物18 g/kg也明显降低肥胖大鼠附睾脂肪质量.但苦瓜乙醇提取物对肥胖大鼠的糖耐量和胰岛素抵抗指数无明显影响.结论 苦瓜乙醇提取物通过抑制肥胖大鼠内脏脂肪聚积和附睾脂肪细胞肥大以及降低空腹血糖浓度发挥减肥和抗糖尿病作用.     

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??OBJECTIVE To study the effect of extract from the stems of Schisandra chinensis(SCE) on high-fat diet (HFD)induced obesity in mice. METHODS The model of HFD induced obese model of C57BL/6J mice for 8 weeks was established. The contents of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (T-CHO), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol(HDL-C) and hepatic triglyceride (TG), total cholesterol (T-CHO), glutathione (GSH)and malondialdehyde(MDA) were measured. The pathological changes with H&E staining and oil red O was observed for investigating the effect of SCE in the obese mice. In addition, the assay of CYP2E1, 4-HNE using immunofluorescence staining and the expression of iNOS and COX-2 protein with Western blot analyzing was measured to explore the effect of SCE on lipid peroxidation and inflammatory response. RESULTS Compared with the HFD group, low and high dose groups of SCE significantly reduced the serum AST, ALT, TG, T-CHO, LDL-C and hepatic TG, TC and MDA levels, elevated the serum HDL-C and hepatic GSH levels and improved liver tissue steatosis, inflammatory infiltration and accumulation of lipid droplets, oxidative stress and inflammatory response. CONCLUSION SCE may improve lipid metabolism in HFD induced obese mice by inhibiting oxidative stress and inflammatory response.     

The Anti‐Obesity Effects of the Dietary Combination of Fermented Red Ginseng with Levan in High Fat Diet Mouse Model

In this study, to evaluate the anti‐obesity effects of fermented red ginseng (FG), levan (L), and their combination (FGL), we investigated their effects on the weights of body, liver and white adipose tissue, lipid profiles, and biomarkers for insulin resistance in high fat diet (HFD)‐induced obese C57BL/6J male mice. Furthermore, the levels of leptin in the serum were measured. FG (150 mg/kg/d), L (100 mg/kg/d), and FGL (150 mg/kg/d of FG plus 100 mg/kg/d of L) were administered orally to mice daily for 11 weeks. After 11 weeks feeding, FGL showed significantly lower body weight and fat mass with decreasing food efficiency ratio than the HFD control mice. In addition, the FGL group was significantly lower in the levels of total cholesterol and fasting blood glucose and score of the homeostatic model assessment of insulin resistance. Furthermore, FGL decreased serum leptin levels compared to the HFD control group. Taken together, FGL showed a significant anti‐obesity effect in HFD‐induced obese mice and prevent insulin and leptin resistance. FGL may be potentially useful for the prevention of obesity. Copyright © 2013 John Wiley & Sons, Ltd.     

Anti-obesity action of Salix matsudana leaves (Part 1). Anti-obesity action by polyphenols of Salix matsudana in high fat-diet treated rodent animals

In preliminary experiments, polyphenol fractions prepared from the leaves of Salix matsudana reduced the elevation of the rat plasma triacylglycerol level at 3 and 4 h after oral administration of a lipid emulsion containing corn oil, at a dose of 570 mg/kg. The present study examined the anti-obesity action of polyphenol fractions of S. matsudana leaves by testing whether the polyphenol fractions prevented the obesity induced by feeding a high-fat diet to female mice for 9 weeks. Body weights at 2-9 weeks and the fi nal parametrial adipose tissue weights were significantly lower in mice fed the high-fat diet with 5% polyphenols of S. matsudana leaves than in those fed the high-fat diet alone. The polyphenols of S. matsudana leaves also significantly reduced the hepatic total cholesterol content, which was elevated in mice fed the high-fat diet alone. In addition, the polyphenol fractions of S. matsudana leaves inhibited palmitic acid uptake into brush border membrane vesicles prepared from rat jejunum and alpha-amylase activity, and their fractions enhanced norepinephrine-induced lipolysis in fat cells. In conclusion, it is suggested that the inhibitory effects of the flavonoid glycoside fraction of S. matsudana leaves on high-fat diet-induced obesity might be due to the inhibition of carbohydrate and lipid absorption from small intestine through the inhibition of alpha-amylase and palmitic acid uptake into small intestinal brush border membrane or by accelerating fat mobilization through enhancing norepinephrine-induced lipolysis in fat cells.     

Regulation of obesity and lipid disorders by herbal extracts from Morus alba, Melissa officinalis, and Artemisia capillaris in high-fat diet-induced obese mice

Melissa officinalis L. (Labiatae), Morus alba L. (Moraceae), and Artemisia capillaris Thunb. (Compositae) are suggested to be involved in the regulation of hyperlipidemia. We hypothesized that Ob-X, a mixture of three herbs, Morus alba, Melissa officinalis and Artemisia capillaris [corrected] improves lipid metabolism, body weight gain and adiposity and that peroxisome proliferator-activated receptor alpha (PPARalpha) is associated with these events. Mice fed a high-fat diet for 12 weeks exhibited increases in body weight gain and adipose tissue mass compared with mice fed a low fat diet. However, feeding a high-fat diet supplemented with Ob-X significantly reduced these effects. Ob-X treatment also decreased the circulating levels of triglycerides and total cholesterol, and inhibited hepatic lipid accumulation. Ob-X supplementation was found to increase the hepatic mRNA levels of PPARalpha target enzymes responsible for fatty acid beta-oxidation. Moreover, Ob-X elevated the endogenous expression of a luciferase reporter gene containing three copies of a PPAR response element (PPRE) in NMu2Li liver cells. These data demonstrate that Ob-X regulates body weight gain, adipose tissue mass, and lipid metabolism in part through changes in the expression of hepatic PPARalpha target genes.     

叶黄素对小鼠急性酒精性肝损伤的保护作用

目的:探讨叶黄素(LU)预处理对酒精所致小鼠急性肝损伤的保护作用。方法:将48只小鼠随机分为4组:对照组、酒精组、20mg/kg及40mg/kg叶黄素预处理组。小鼠连续灌胃LU 8d,第4d给予LU l h后灌胃56度红星二锅头12ml/kg。连续灌胃酒精5d。在末次给药后24h采血,测定血清谷草转氨酶(AST)、谷丙转氨酶(ALT)。采血后处死动物,剖取肝脏,测定肝脏系数、肝匀浆丙二醛(MDA)、谷胱甘肽(GSH)和超氧化物歧化酶(SOD)活力,同时观察肝组织病理结构。结果:模型组小鼠血清ALT、AST活性明显高于对照组,肝组织匀浆中MDA含量显著增加,而GSH含量及SOD活性显著下降。给予叶黄素20mg/kg及40mg/kg均可降低肝损伤小鼠血清ALT、AST活性,而40mg/kg叶黄素还可降低肝组织匀浆MDA水平,提高GSH含量及SOD活性,并可改善酒精损伤大鼠肝病理组织结构。结论:叶黄素可通过抗氧化作用减轻酒精诱导的小鼠肝损伤。     

Regulation of obesity and lipid disorders by extracts from Angelica acutiloba root in high-fat diet-induced obese rats

The aim of this study was to investigate the antiobesity and antihyperlipidemic effects of Angelica acutiloba root (Japanese Dong Quai). High‐fat diet (HFD)‐induced obese rats were treated orally with the polyphenolic‐rich extract of Angelica acutiloba root (AARE) once daily for 8 weeks. The AARE (300 mg/kg per day) supplementation significantly lowered body weight gain, visceral fat‐pad weights and plasma lipid levels, as well as the coronary artery risk index and the atherogenic index of HFD‐fed rats. The AARE caused dose related reductions in the hepatic triglyceride and cholesterol contents, as well as lowered hepatic lipid droplet accumulation and epididymal adipocyte size in the HFD‐fed rats. The AARE reversed the HFD‐induced down‐regulation of the hepatic peroxisome proliferator activated receptor‐α (PPARα). The HFD‐induced decreases of the hepatic protein level of acyl‐CoA oxidase (ACO), and the cytochrome P450 isoform 4A1 (CYP4A1) was up‐regulated by AARE. The elevated expressions of hepatic sterol regulatory element binding proteins (SREBPs) of HFD‐fed rats were lowered by AARE. These results suggest that AARE attenuated visceral fat accumulation and improved hyperlipidemia in HFD‐induced obesity by increasing lipid metabolism through the down‐regulation of SREBPs and enhanced the expression of ACO and CYP4A1 in the liver, which was likely mediated by up‐regulation of the expression of hepatic PPARα. Copyright © 2011 John Wiley & Sons, Ltd.     

Euonymus alatus prevents the hyperglycemia and hyperlipidemia induced by high-fat diet in ICR mice

Euonymus alatus (EA), known as a Gui Jeon Wu in China, has been used as a folk medicine for regulating blood circulation, relieving pain, eliminating blood clot, and treating dysmenorrhea in Asian countries. Although EA has anecdotally ascertained to show the anti-hyperglycemic activity by enhancing insulin secretion, there is no sufficient experimental evidence for anti-hyperglycemic activity of EA. The purpose of this study was to investigate the preventive effect of 50% ethanol extract of EA in high-fat diet-induced hyperglycemic and hyperlipidemic ICR mice. At 6 week old, the ICR mice were randomly divided into five groups; two control and three treatment groups. The control mice was to receive either a regular diet (RD) or high-fat diet (HFD), and the treatment groups were fed a high-fat diet with either 350, 700 mg/kg of EA (EA350 and EA700) or 250 mg/kg of metformin (MET250) for a 10-week period. EA not only reduced body weight in a dose dependent manner, but also corrected associated hyperinsulinemia and hyperlipidemia. EA exerted beneficial effects on glucose and lipid homeostasis in diabetes that are not secondary to its ability to decrease food intake but its specific effects on hepatic lipogenesis related genes (SREBPla, FAS, GAPT) and PPAR-gamma gene expression in periepididymal fat. Taken together, the combined effect of EA to reduce plasma glucose and lipid levels, and reduce the deposition of triglyceride in the liver are indicative of a marked improvement in obesity-related diabetes and non-alcoholic fatty liver disease.     

Decursin, an active compound isolated from Angelica gigas, inhibits fat accumulation, reduces adipocytokine secretion and improves glucose tolerance in mice fed a high-fat diet

Decursin (De), an active component of Angelica gigas, is known to exert anticancer and neuroprotective effects. However, its antiobesity and antidiabetic potential has not yet been investigated. This study evaluated the antiobesity effect of decursin, particularly focusing on its ability to inhibit adipocyte differentiation in 3T3-L1 cells. Decursin treatment resulted in the inhibition of adipocyte differentiation and the expression of fatty acid synthase. The study further investigated these antiobesity effects using mice fed a normal diet (ND), a high-fat diet (HFD) and a HFD plus decursin 200 mg/kg diet (HFD + De) for 7 weeks. Mice administered HFD plus decursin showed a drastic decrease in weight gain, triglyceride content, total cholesterol content and fat size compared with those that received the HFD alone; this was observed despite similar quantities of total food intake. Furthermore, decursin improved glucose tolerance in mice fed a HFD. Finally, administration of decursin along with the HFD significantly reduced the secretion of HFD-induced adipocytokines such as leptin, resistin, IL-6 and MCP-1. These results suggest that decursin might be useful for the treatment of obesity and diabetes.     

Parkinsonia aculeata aqueous extract fraction: biochemical studies in alloxan-induced diabetic rats

The antidiabetic effect of Parkinsonia aculeata water soluble fraction (WSF) made of aerial parts of the plant (leaves and flowers) was investigated in alloxan diabetic rats. Its effect was compared with that of insulin (positive control). The physico-metabolic parameters measured were: body weight, food and liquid intake, urinary volume, hepatic glycogen, serum glucose, total cholesterol, HDL-cholesterol, triglycerides, urinary glucose and urea, and the weight of epididymal adipose tissue, liver, kidneys and the skeletal muscles (soleus and extensor digitorum longus). Oral administration of WSF (125 or 250 mg/kg) for 16 days exhibited a significant reduction in serum and urinary glucose, urinary urea, total cholesterol, HDL-cholesterol and triglycerides in alloxan diabetic rats. An improvement of hepatic glycogen, a decrease of liquid and food intake, and a significantly positive actions in the weight of skeletal muscles (soleus and extensor digitorum longus) and kidneys were also observed, but just diabetic group treated with WSF at a dose of 125 mg/kg showed significant reduction in urinary volume, body weight, an improvement of epididymal adipose tissue and a positive action in liver weight. The effects of WSF on the physico-metabolic parameters was comparable to those observed in diabetic insulin treated group. The results of this work suggest that P. aculeate may have new clinical significant choice in diabetes mellitus illness, and could explain the basis for its traditional use to manage diabetes-related complications by rural community of northeast of Brazil.     

津力达颗粒对高脂饮食诱导的肥胖小鼠代谢紊乱及FGF21/AMPK信号通路的影响

目的研究津力达颗粒对高脂饮食诱导的肥胖小鼠代谢紊乱及成纤维细胞生长因子21(fibroblast growth factor 21,FGF21)/磷酸腺苷活化蛋白激酶(AMP-dependent/activated protein kinase,AMPK)信号通路的影响。方法C57BL/6J小鼠随机分为对照组、模型组、津力达颗粒(3.8g/kg)组,对照组小鼠喂食标准饲料,其余各组小鼠喂食高脂饲料;给予津力达颗粒进行干预后,每周称定小鼠体质量并记录小鼠日摄食、饮水量;ELISA法检测各组小鼠血清中三酰甘油(triglycerides,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)和高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)水平;苏木素-伊红(HE)染色法观察各组小鼠肝脏、脂肪组织病理变化;通过腹膜内葡萄糖耐量实验测定各组小鼠血糖水平;qRT-PCR和Westernblotting法检测小鼠肝脏和脂肪组织中FGF21/AMPK通路相关基因和蛋白的表达。结果与模型组比较,津力达颗粒组小鼠体质量、棕色脂肪质量、白色脂肪质量、肝脏质量显著降低(P<0.05、0.01、0.001);血清TG、LDL-C水平显著降低(P<0.01、0.001),HDL-C水平显著升高(P<0.001);血糖水平显著降低(P<0.01、0.001);肝脏FGF21、成纤维生长因子受体1(fibroblast growth factor receptors 1,FGFR1)m RNA表达水平显著升高(P<0.05、0.01);肝脏FGF21、p-AMPK、p-AMPK/AMPK蛋白表达水平明显升高(P<0.05、0.001),肝脏AMPK、Klotho、沉默信息调节因子1(silentinformationregulator1,SIRT1)蛋白水平明显降低(P<0.05);脂肪FGF21 mRNA表达水平显著升高(P<0.01),脂肪FGFR1、AMPK、p-AMPK蛋白表达水平明显升高(P<0.05、0.001)。结论津力达颗粒可以通过调节FGF21及其蛋白受体复合物(FGFR1/β-Klotho),进一步激活AMPK信号通路,改善高脂饮食诱导的代谢紊乱,为津力达颗粒在代谢综合征的临床应用提供依据。     

小檗碱对兔血脂代谢及维生素D受体和胰岛素诱导基因2基因表达的影响

目的研究小檗碱对高脂模型兔血脂代谢的影响,并探讨其调血脂作用是否与维生素D受体(vitamin D receptor,VDR)、胰岛素诱导基因2(insulin-induced gene 2,Insig-2)的表达变化有关。方法雄性新西兰大耳白兔40只随机分为对照组、模型组、阳性药非诺贝特(30 mg/kg)组和小檗碱低、高剂量(28、112 mg/kg)组。兔喂饲高脂饲料8周建立高脂模型,给药8周后测定各组兔血清中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白-胆固醇(LDL-C)、高密度脂蛋白-胆固醇(HDL-C)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)和脂蛋白a(LPa)等指标的水平。RT-PCR法检测脂肪组织中VDR和Insig-2基因表达的变化。结果与对照组比较,模型组兔血清TC、TG、LDL-C、ApoB及LPa水平明显升高(P<0.05),而ApoA1水平则明显降低(P<0.05);经小檗碱处理后,兔血清中TC、TG、LDL-C、ApoB及LPa的水平较模型组显著降低(P<0.05),同时ApoA1水平则明显升高(P<0.05);RT-PCR检测结果显示,小檗碱干预后兔脂肪组织中VDR、Insig-2 mRNA的表达较模型组显著升高(P<0.05),且低剂量小檗碱的效果更明显。结论小檗碱具有明显的调血脂作用,其机制可能是通过上调脂肪组织VDR和Insig-2 mRNA表达来实现的。     

麦冬皂苷D对高脂饲养ApoE~(-/-)小鼠血脂及肠道菌群的影响

目的研究麦冬皂苷D(ophiopogonin D,OP-D)对高脂饲养ApoE~(-/-)小鼠血脂及肠道菌群的影响。方法选取6周龄雄性ApoE~(-/-)小鼠24只,随机均分为对照组、模型组、OP-D组[0.5 mg/(kg·d)]和辛伐他汀组[5 mg/(kg·d)];雄性C57BL/6小鼠6只为空白组。造模12周后,连续给药12周。给药结束后收集小鼠新鲜粪便,检测菌群情况;分离小鼠血清检测血脂水平,制备肝脏切片染色观察损伤情况。结果 OP-D能够降低小鼠因高脂饮食引起的体质量增加,抑制总胆固醇(TC)和三酰甘油(TG)升高,改善肝脂肪变性,并多种水平上调控肠道菌群失调。结论 OP-D可能通过改善高脂饲养的ApoE~(-/-)小鼠肠道菌群失调影响其血脂水平和肝脂肪变性。     

乌药叶总黄酮对高脂血症脂肪肝小鼠模型的降脂作用

目的考察乌药叶总黄酮的降脂作用。方法利用高脂饲料建立小鼠高脂血症脂肪肝动物模型,以不同剂量(50,100,200 mg/kg)的乌药叶总黄酮给小鼠每天灌胃,连续4周后检测血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)及高密度脂蛋白胆固醇(HDLC)水平。同时观察其对肝脏脂质系数(肝脏TC、TG)、脂肪系数、动脉硬化指数(AI)、体重以及肝组织病理变化的影响。并利用棕榈酸钠(Sodium palmi-tate,PA)诱导人肝癌HepG2细胞发生脂肪变性,通过油红O染色法检测乌药叶总黄酮对细胞内脂滴沉积的影响。结果在小鼠高脂血症性脂肪肝动物模型中,乌药叶总黄酮的中、高剂量均能一定程度降低血清TC、TG、LDLC水平,其中高剂量组TC与模型组相比有显著性差异。乌药叶总黄酮还可以剂量依赖性地降低肝脏脂质系数、脂肪系数、AI及体重,并减轻肝脏的脂肪变性程度。随着乌药叶总黄酮浓度的增加,HepG2细胞中脂滴形成明显减少。结论乌药叶总黄酮有较明显的降血脂作用,可改善肝细胞脂肪变性,对脂肪肝有较好的治疗作用。     

The Beneficial Effect of Anthocyanidin‐Rich Vitis vinifera L. Grape Skin Extract on Metabolic Changes Induced by High‐Fat Diet in Mice Involves Antiinflammatory and Antioxidant Actions

We hypothesized that a polyphenol‐rich extract from Vitis vinifera L. grape skin (GSE) may exert beneficial effects on obesity and related metabolic disorders induced by a high‐fat diet (HFD). C57/BL6 mice were fed a standard diet (10% fat, control, and GSE groups) or an HFD (60% fat, high fat (HF), and HF + GSE) with or without GSE (200 mg/kg/day) for 12 weeks. GSE prevented weight gain; dyslipidemia; insulin resistance; the alterations in plasma levels of leptin, adiponectin, and resistin; and the deregulation of leptin and adiponectin expression in adipose tissue. These beneficial effects of GSE may be related to a positive modulation of insulin signaling proteins (IR, pIRS, PI3K, pAKT), pAMPK/AMPK ratio, and GLUT4 expression in muscle and adipose tissue. In addition, GSE prevented the oxidative damage, evidenced by the restoration of antioxidant activity and decrease of malondialdehyde and carbonyl levels in muscle and adipose tissue. Finally, GSE showed an anti‐inflammatory action, evidenced by the reduced plasma and adipose tissue inflammatory markers (TNF‐α, IL‐6). Our results suggest that GSE prevented the obesity and related metabolic disorders in HF‐fed mice by regulating insulin sensitivity and GLUT4 expression as well as by preventing the oxidative stress and inflammation in skeletal muscle and adipose tissue. Copyright © 2017 John Wiley & Sons, Ltd.