Effects of green tea polyphenol (-)-epigallocatechin-3-gallate on newly developed high-fat/Western-style diet-induced obesity and metabolic syndrome in mice

The aim of this study was to investigate the effects of (-)-epigallocatechin-3-gallate (EGCG) on newly developed high-fat/Western-style diet-induced obesity and symptoms of metabolic syndrome. Male C57BL/6J mice were fed a high fat/Western-style (HFW; 60% energy as fat and lower levels of calcium, vitamin D(3), folic acid, choline bitartrate, and fiber) or HFW with EGCG (HFWE; HFW with 0.32% EGCG) diet for 17 wks. As a comparison, two other groups of mice fed a low-fat diet (LF; 10% energy as fat) and high-fat diet (HF; 60% energy as fat) were also included. The HFW group developed more body weight gain and severe symptoms of metabolic syndrome than the HF group. The EGCG treatment significantly reduced body weight gain associated with increased fecal lipids and decreased blood glucose and alanine aminotransferase (ALT) levels compared to those of the HFW group. Fatty liver incidence, liver damage, and liver triglyceride levels were also decreased by the EGCG treatment. Moreover, the EGCG treatment attenuated insulin resistance and levels of plasma cholesterol, monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP), interlukin-6 (IL-6), and granulocyte colony-stimulating factor (G-CSF). Our results demonstrate that the HFW diet produces more severe symptoms of metabolic syndrome than the HF diet and that the EGCG treatment can alleviate these symptoms and body fat accumulation. The beneficial effects of EGCG are associated with decreased lipid absorption and reduced levels of inflammatory cytokines.     

Green and black tea suppress hyperglycemia and insulin resistance by retaining the expression of glucose transporter 4 in muscle of high-fat diet-fed C57BL/6J mice

To investigate the preventive effects of tea on hyperglycemia and insulin resistance, male C57BL/6J mice were given a high-fat diet containing 29% lard and also green or black tea ad libitum for 14 weeks. Both teas suppressed body weight gain and deposition of white adipose tissue caused by the diet. In addition, they improved hyperglycemia and glucose intolerance by stimulating glucose uptake activity accompanied by the translocation of glucose transporter (GLUT) 4 to the plasma membrane in muscle. Long-term consumption of the high-fat diet reduced levels of insulin receptor β-subunit, GLUT4 and AMP-activated protein kinase α in muscle, and green and black tea suppressed these decreases. The results strongly suggest that green and black tea suppress high-fat diet-evoked hyperglycemia and insulin resistance by retaining the level of GLUT4 and increasing the level of GLUT4 on the plasma membrane in muscle.     

Amelioration of obesity and glucose intolerance in high-fat-fed C57BL/6 mice by anthocyanins and ursolic acid in Cornelian cherry (Cornus mas)

Much attention has been focused on food that may be beneficial in preventing diet-induced body fat accumulation and possibly reduce the risk of diabetes and heart disease. Cornelian cherries (Cornus mas) are used in the preparation of beverages in Europe and also to treat diabetes-related disorders in Asia. In this study, the most abundant bioactive compounds in C. mas fruits, the anthocyanins and ursolic acid, were purified, and their ability to ameliorate obesity and insulin resistance in C57BL/6 mice fed a high-fat diet was evaluated. Mice were initially fed a high-fat diet for 4 weeks and then switched to a high-fat diet containing anthocyanins (1 g/kg of high-fat diet) and ursolic acid (500 mg/kg of high-fat diet) for an additional 8 weeks. The high-fat diet induced glucose intolerance, and this was prevented by anthocyanins and ursolic acid. The anthocyanin-treated mice showed a 24% decrease in weight gain. These mice also showed decreased lipid accumulation in the liver, including a significant decrease in liver triacylglycerol concentration. Anthocyanin and ursolic acid treated mice exhibited extremely elevated insulin levels. Both treatments, however, showed preserved islet architecture and insulin staining. Overall, these data suggest that anthocyanins and ursolic acid purified from C. mas fruits have biological activities that improve certain metabolic parameters associated with diets high in saturated fats and obesity.     

Lower weight gain and hepatic lipid content in hamsters fed high fat diets supplemented with white rice protein, brown rice protein, soy protein, and their hydrolysates

The physiological effects of the hydrolysates of white rice protein (WRP), brown rice protein (BRP), and soy protein (SP) hydrolyzed by the food grade enzyme, alcalase2.4 L, were compared to the original protein source. Male Syrian Golden hamsters were fed high-fat diets containing either 20% casein (control) or 20% extracted proteins or their hydrolysates as the protein source for 3 weeks. The brown rice protein hydrolysate (BRPH) diet group reduced weight gain 76% compared with the control. Animals fed the BRPH supplemented diet also had lower final body weight, liver weight, very low density lipoprotein cholesterol (VLDL-C), and liver cholesterol, and higher fecal fat and bile acid excretion than the control. Expression levels of hepatic genes for lipid oxidation, PPARα, ACOX1, and CPT1, were highest for hamsters fed the BRPH supplemented diet. Expression of CYP7A1, the gene regulating bile acid synthesis, was higher in all test groups. Expression of CYP51, a gene coding for an enzyme involved in cholesterol synthesis, was highest in the BRPH diet group. The results suggest that BRPH includes unique peptides that reduce weight gain and hepatic cholesterol synthesis.     

Whole berries versus berry anthocyanins: interactions with dietary fat levels in the C57BL/6J mouse model of obesity

Male C57BL/6J mice received diets with either 10% of calories from fat (LF) or a high-fat diet [45% (HF45) or 60% (HF60) calories from fat] for 92 days (expt 1) or 70 days (expt 2). These were given with or without freeze-dried powders from whole blueberries (BB) or strawberries (SB) (expt 1) or purified anthocyanin extracts from BB or SB (expt 2). Body composition was determined utilizing Echo MRI. Berries added to the LF diet did not alter weight gain, final body weights, body fat, or protein (percent body weight) or diet (grams) or energy (kilocalories) intake. However, in both HF45- and HF60-fed mice, weight gain, final weights, body fat (percent), and epididymal fat weights increased and body protein decreased ( p < 0.01) compared to LF mice. In mice fed HF45 diet plus BB, body weight gains, body fat (percent of BW), and epididymal fat weights were significantly greater than those in the HF45-fed controls, whereas weights of mice fed SB HF were similar to those of HF controls. SB or BB feeding did not alter glucose tolerance, although glucose tolerance decreased with age and in HF45 versus LF mice. Baseline plasma glucose was lower in SB- versus HF45-fed mice. After 8 weeks, mice fed the HF60 diet plus purified anthocyanins from BB in the drinking water had lower body weight gains and body fat than the HF60-fed controls. Anthocyanins fed as the whole blueberry did not prevent and may have actually increased obesity. However, feeding purified anthocyanins from blueberries or strawberries reduced obesity.     

Green Tea Prevents Obesity by Increasing Expression of Insulin-like Growth Factor Binding Protein-1 in Adipose Tissue of High-Fat Diet-Fed Mice

It is known that green tea has the ability to prevent obesity, but the underlying molecular mechanism is not fully understood to date. A preventive mechanism of green tea on obesity in C57BL/6 mice fed a high-fat (HF) diet was investigated by evaluating the expression levels of obesity-related proteins in mesenteric white adipose tissue by using protein array. An increase in the expression level of insulin-like growth factor binding protein (IGFBP)-1 by green tea was found in the white adipose tissues of both control and HF diet-fed mice by protein array and confirmed by Western blot. Moreover, the expression level was negatively correlated with adipose tissue weight. In 3T3-L1 adipocytes, treatment with green tea and its major polyphenol, (-)-epigallocatechin gallate, induced the expression of IGFBP-1 in a dose-dependent manner by Western blot. In conclusion, IGFBP-1 in adipose tissue is a novel molecule target for the prevention of obesity by green tea.     

Petalonia binghamiae extract and its constituent fucoxanthin ameliorate high-fat diet-induced obesity by activating AMP-activated protein kinase

In this study, we investigated the antiobesity properties of Petalonia binghamiae extract (PBE) in mice in which obesity was induced with a high-fat diet (HFD). PBE administration (150 mg/kg/day) for 70 days decreased body weight gain, adipose tissue weight, and the serum triglyceride level in mice fed a HFD. PBE reduced serum levels of glutamic pyruvic transaminase and glutamic oxaloacetic transaminase as well as the accumulation of lipid droplets in the liver. PBE restored the HFD-induced decrease in phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in epididymal adipose tissue. PBE increased the phosphorylation of AMPK and ACC and decreased the expression of SREBP1c in mature 3T3-L1 adipocytes. In addition, we further explored the active compound responsible for AMPK activation by PBE in 3T3-L1 adipocytes. Fucoxanthin isolated from PBE increased the phosphorylation of AMPK and ACC with increasing LKB1 phosphorylation in mature 3T3-L1 adipocytes. Taken together, these data suggest that PBE (or fucoxanthin) exert improving effects on HFD-induced obesity by promoting β-oxidation and reducing lipogenesis.     

葡萄籽原花青素对肥胖大鼠肠粘膜的影响

为探究葡萄籽原花青素(GSP)对营养肥胖模型大鼠肠粘膜通透性的影响,本试验设置了正常、模型、低剂量、中剂量及高剂量5个处理组,其中正常组投喂普通饲料,灌胃3 mL蒸馏水;模型组和低、中、高剂量组选用32只高脂饲料诱导的肥胖大鼠,模型组灌胃蒸馏水,低、中、高剂量组分别灌胃75、162.5、250 mg·kg^-1BW·d^-1GSP,灌胃处理6周再禁食12 h后处死,经解剖后测定各处理组大鼠的生理生化相关指标。结果表明,高脂饲料造模成功率48.75%;与模型组相比,低、中、高剂量组大鼠D-乳酸、乳果糖/甘露醇排出率显著降低,回肠绒毛高度/隐窝深度、紧密连接蛋白Occludin和 ZO-1 表达量显著升高;高剂量组大鼠的回肠杯状细胞数显著升高。综上,葡萄籽原花青素可以改善肥胖应激导致的大鼠肠道粘膜屏障损伤,这在一定程度上揭示了葡萄籽原花青素减肥降脂的作用机理。     

Lupane-type saponins from leaves of Acanthopanax sessiliflorus and their inhibitory activity on pancreatic lipase

Three known saponins, chiisanoside, 11-deoxyisochiisanoside, and isochiisanoside, and one novel saponin, 3,4-seco-4(23),20(29)-lupadiene-3,28-dioic acid 28-O-alpha-l-rhamnopyranosyl (1-->4)-beta-d-glucopyranosyl (1-->6)-beta-d-glucopyranoside, referred to as sessiloside, were isolated from a hot water extract of Acanthopanax sessiliflorus leaves. All of these saponins were lupane-type triterpene triglycosides, and their concentrations were 4.1, 1.0, 0.5, and 0.4% (w/w) of the total extract, respectively. Sessiloside and chiisanoside inhibited pancreatic lipase activity in vitro, and addition of the saponin-rich fraction to a high-fat diet suppressed the body weight gain of mice. The possibility of application of the lupane-type saponins from A. sessiliflorus leaves to the treatment of obesity is discussed.     

Muscadine Grape ( Vitis rotundifolia ) and Wine Phytochemicals Prevented Obesity-Associated Metabolic Complications in C57BL/6J Mice

The objective of this study was to determine the effects of muscadine grape or wine (cv. Noble) phytochemicals on obesity and associated metabolic complications. Muscadine grape or wine phytochemicals were extracted using Amberlite FPX66 resin. Male C57BL/6J mice were given a low-fat diet (LF, 10% kcal fat), high-fat diet (HF, 60% kcal fat), HF + 0.4% muscadine grape phytochemicals (HF+MGP), or HF + 0.4% muscadine wine phytochemicals (HF+MWP) for 15 weeks. At 7 weeks, mice fed HF+MGP had significantly decreased body weights by 12% compared to HF controls. Dietary MGP or MWP supplementation reduced plasma content of free fatty acids, triglycerides, and cholesterol in obese mice. Inflammation was alleviated, and activity of glutathione peroxidase was enhanced. Consumption of MGP or MWP improved insulin sensitivity and glucose control in mice. Thus, consumption of muscadine grape and wine phytochemicals in the diet may help to prevent obesity-related metabolic complications.     

Critical role of peroxisome proliferator activated receptor-δ on body fat reduction in C57BL/6J and human apolipoprotein E2 transgenic mice fed delipidated soybean

The consumption of soy protein and fiber reduces body fat accumulation; however, the mechanism of this effect has not been clearly understood. We investigated the antiobesogenic effect of soy protein and fiber in two different mouse models. Normolipidemic nonobese C57BL/6J and hyperlipidemic obese human apolipoprotein E2 transgenic mice were fed either delipidated soybean (DLSB) containing soy protein and fiber or a control diet. The DLSB-fed mice showed a significant reduction in body weight gain and adiposity compared with controls, in both C57BL/6J and apoE2 mice. All metabolic parameters were significantly improved in the DLSB group compared with controls: total cholesterol, low-density lipoprotein cholesterol, insulin, and leptin levels were significantly reduced. Adiponectin concentrations were significantly elevated, and glucose tolerance was improved. In both types of DLSB-fed mice, the specific induction of PPAR-δ protein expression was evident in muscle and adipose tissues. The expression of PPAR-δ target genes in the DLSB-fed mice was also significantly altered. Acetyl-CoA carboxylase-1 and fatty acid synthase levels in adipose tissue were downregulated, and uncoupling protein-2 in muscle was upregulated. Intestinal expression of fatty acid transport protein-4, cluster of differentiation-36, and acyl-CoA synthetase were significantly downregulated. We propose that marked activation of PPAR-δ is the primary mechanism mediating the antiobesogenic effect of soybean and that PPAR-δ has multiple actions: induction of thermogenesis in muscle, reduction of fatty acid synthesis in adipose tissue, and reduction of fatty acid uptake in intestinal tissue.     

Effect of Bran Extract from Pigmented Rice Superjami on the Lipid and Glucose Metabolisms in a Postmenopause‐Like Model of Ovariectomized Rats

The effect of rice bran ethanolic extract from Superjami, a new blackish‐purple pigmented cultivar, on the lipid and glucose metabolisms in a postmenopausal‐like model of ovariectomized rats was investigated. Sprague‐Dawley female rats were subjected to either bilateral ovariectomy or a sham operation and randomly divided into three dietary groups (n = 6): sham‐operated fed with normal diet (SHAM), ovariectomized fed with normal diet (OVX‐AIN76), and ovariectomized fed with normal diet supplemented with Superjami bran extract (OVX‐SJ). The OVX‐AIN76 group showed significantly higher body weight, triglyceride, total cholesterol, blood glucose, and insulin than the SHAM group. On the other hand, supplementation of Superjami bran extract markedly reduced the body weight gain and improved the lipid and glucose profiles in ovariectomized rats through inhibition of hepatic lipogenesis and adipokine production and modulation of glucose‐regulating enzyme activities. These findings demonstrate that extracts from Superjami bran may be useful in the prevention and management of postmenopause‐induced hyperlipidemia and hyperglycemia.     

Barley intake induces bile acid excretion by reduced expression of intestinal ASBT and NPC1L1 in C57BL/6J mice

To investigate the hypocholesterolemic mechanism of barley in vivo, six-week-old C57BL/6J mice were fed a high-fat diet (HFD) or high-fat diet containing barley (HFD-B) for seven weeks. Total and LDL cholesterol concentrations were significantly reduced in the HFD-B group while fecal cholesterol and bile acid was increased. Real-time PCR and immunoblot analysis revealed the induction of FXR expression, which in turn suppressed the expression of ASBT and NPC1L1 in the HFD-B group compared with the controls. In the liver, the expression of HMG-CoA reductase was significantly reduced while LDL receptor expression was unaltered in the HFD-B group compared with the controls. Our data suggest that the hypocholesterolemic effects of barley are primarily the result of reduced dietary cholesterol uptake and bile acid resorption. Reduced expression of intestinal ASBT and NPC1L1 may play a key role in the regulation of dietary cholesterol and bile acid metabolism in mice consuming a diet containing barley.     

Effects of cocoa extract on glucometabolism, oxidative stress, and antioxidant enzymes in obese-diabetic (Ob-db) rats

In this present study, we investigated the effects of cocoa extract containing polyphenols and methylxanthines prepared from cocoa powder on the biochemical parameters of obese-diabetic (Ob-db) rats. Obese-diabetic (Ob-db) rats were developed using a high-fat diet (49% fat, 32% carbohydrate, and 19% protein from total energy, kcal) for 3 months, followed by a low dose (35 mg/kg body weight) streptozotocin (STZ) injection. Cocoa extract (600 mg/kg body weight/day) was given to the rats for 4 weeks. The results indicated that there were no significant differences in fasting plasma glucose and insulin level after 4 weeks of cocoa extract administration. Oral glucose tolerance test revealed that cocoa supplementation in Ob-db rats significantly (p < 0.05) reduced plasma glucose at 60 and 90 min compared to unsupplemented Ob-db rats. Plasma free fatty acid and oxidative stress biomarker (8-isoprostane) were significantly (p < 0.05) reduced after cocoa supplementation. Superoxide dismutase activity was enhanced in Ob-db compared to that in nonsupplemented rats. However, no change was observed in catalase activity. The results showed that cocoa supplementation had an effect on postprandial glucose control but not for long term (4 weeks). Moreover, cocoa supplementation could reduce circulating plasma free fatty acid and 8-isoprostane and may enhance the antioxidant defense system.     

Mulberry water extracts possess an anti-obesity effect and ability to inhibit hepatic lipogenesis and promote lipolysis

Obesity plays a critical role in dyslipidemia and related disorders. Mulberry water extracts (MWEs) contain polyphenols, including gallic acid, chlorogenic acid, rutin, and anthocyanins. In this study, using 6-week-old male hamsters, we investigated the anti-obese effect of MWEs. After 12 weeks of treatment, MWEs lowered high-fat diet (HFD)-induced body weight and visceral fat, accompanied with hypolipidemic effects by reducing serum triacylglycerol, cholesterol, free fatty acid, and the low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio (n=8 for each group). MWEs decreased hepatic lipids, thus protected livers from impairment. The hepatic peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1 were elevated, while fatty acid synthase and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase were reduced by MWEs, indicating that MWEs regulated lipogenesis and lipolysis, which exerted the anti-obese and hypolipidemic effects. Noticeably, MWEs showed both efficacy and safety in vivo. In concluson, MWEs can be used to reduce body weight, serum, and liver lipids.     

Effect of chitosan, O-carboxymethyl chitosan, and N-[(2-hydroxy-3-N,N-dimethylhexadecyl ammonium)propyl] chitosan chloride on overweight and insulin resistance in a murine diet-induced obesity

Two water-soluble chitosan derivatives, O-carboxymethyl chitosan (O-CM-chitosan) and N-[(2-hydroxy-3-N,N-dimethylhexadecyl ammonium)propyl] chitosan chloride (N-CQ-chitosan), were prepared, and the therapeutic effects of chitosan, O-CM-chitosan, and N-CQ-chitosan on insulin resistance were simultaneously evaluated by rats fed on a high-fat diet. The parameters of high-fat diet-induced rats indicated that chitosan and its two derivatives not only have low cytotoxicity but can control overnutrition by fat and achieve insulin resistance therapy. However, the results in experiment in vivo showed that the therapeutic degree varied by the molecular weight and surface charge of chitosan, O-CM-chitosan, and N-CQ-chitosan. N-CQ-chitosan with a MW of 5 × 10(4) decreased body weight, the ratio of fat to body weight, triglyceride, fasting plasma glucose, fasting plasma insulin, free fatty acid, and leptin by 11, 17, 44, 46, 44, 87, and 64% and increased fecal lipid by 95%, respectively.     

Effects of konjac glucomannan on putative risk factors for colon carcinogenesis in rats fed a high-fat diet

The aim of this study was to determine effects of konjac glucomannan (KGM) in a high fat corn oil diet on risk factors of colon carcinogenesis, that is, fecal β-glucuronidase, mucinase, and bile acids, and on preventive factors, that is, fecal microflora and cecal short-chain fatty acids (SCFAs). Sprague-Dawley rats (n = 8 animals per group) were fed a normal-fat fiber-free (5% corn oil, w/w) or high-fat (25% corn oil, w/w) diet containing no fiber, KGM (5%, w/w), or inulin (5%, w/w, as a prebiotic control) for 4 weeks. Results indicated that the high-fat fiber-free diet significantly elevated the fecal β-glucuronidase and mucinase activities and total bile acid concentration and decreased cecal SCFA contents, as compared with its normal-fat counterpart. The incorporation of KGM, as well as inulin, into the high-fat fiber-free diet beneficially reduced the fecal β-glucuronidase and mucinase activities and lithocholic acid (secondary bile acid) concentration. Although KGM elevated the daily fecal total bile acid excretion, the change was due to the primary, instead of the secondary, bile acids. In addition, KGM beneficially promoted the daily fecal excretion of bifidobacteria and lactobacilli and cecal SCFA contents, as compared with the high-fat fiber-free diet. Therefore, the present study suggests that KGM potentially attenuated the high fat-induced risk in colon carcinogenesis.     

浒苔多酚对肥胖小鼠血脂代谢及肠道菌群的调节作用

为了研究浒苔多酚(Enteromorpha prolifera polyphenols, EPP)对高脂饮食诱导小鼠肥胖的预防作用,将24只C57BL/6J小鼠分为4组,即空白对照组、模型对照组、低剂量浒苔多酚处理组(100 mg·kg^-1·d^-1)以及高剂量浒苔多酚处理组(300 mg·kg^-1·d^-1),连续灌胃14周,考察不同剂量浒苔多酚干预对肥胖小鼠生理生化指标以及肠道菌群数量和结构的影响。结果表明,EPP能抑制肥胖小鼠体重增长,降低血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇浓度(LDL-C)、丙二醛(MDA)、谷草转氨酶(AST)和谷丙转氨酶(ALT)浓度,增加高密度脂蛋白胆固醇(HDL-C)浓度,提高超氧化物歧化酶(SOD)、过氧化氢酶(CAT)以及谷胱甘肽过氧化物酶(GSH-Px)活性。此外,EPP干预可提高有益菌如拟杆菌属(Bacteroides)、艾克曼菌属(Akkermansia)及副杆菌属(Parabacteroides)的相对丰度,促进短链脂肪酸(SCFAs)分泌;降低有害菌如瘤胃球菌属(Ruminococcaceae)及颤螺菌属(Oscillospira)的相对丰度。因此,浒苔多酚作为功能性食品成分能够减轻高脂饮食诱导的小鼠肥胖症状。本研究为浒苔多酚作为海洋资源的开发与利用提供了理论依据与数据支撑。     

Licochalcone A prevents adipocyte differentiation and lipogenesis via suppression of peroxisome proliferator-activated receptor γ and sterol regulatory element-binding protein pathways

Licochalcone A (LA) has been shown to exert multiple pharmacological effects, including anti-inflammatory, antiparasitic, antifungal, anticancer, and osteogenic activities. The present study investigated the ability of LA to suppress the differentiation of 3T3-L1 preadipocytes, and its antiobesity activity was explored using high fat diet (HFD)-fed ICR mice. During the terminal differentiation process, 3T3-L1 preadipocytes were treated with LA, and the lipid contents were quantified along with any changes in the expression of biomarkers associated with adipocyte differentiation and lipogenesis. The results show that LA significantly reduced lipid accumulation and down-regulated the expression of peroxisome proliferator-activated receptor γ, CCAAT/enhancer binding protein α, sterol regulatory element-binding protein 1c, and their target genes (fatty acid binding protein, fatty acid synthase, stearoyl-CoA desaturase 1, and glycerol-3-phosphate acyltransferase). In an animal study, body weight, triglyceride, cholesterol, and nonesterified fatty acid levels in the group given 10 mg/kg LA were significantly decreased by 14.0, 48.2, 58.9, and 73.5%, respectively. Transverse microcomputed tomography indicated that visceral fat depots in LA-treated mice were markedly reduced when compared with those of the HFD control group. In summary, these results suggest that LA exerts an antiobesity effect and that it is a candidate for future clinical trials.