TRPV1 Agonist Monoacylglycerol Increases UCP1 Content in Brown Adipose Tissue and Suppresses Accumulation of Visceral Fat in Mice Fed a High-Fat and High-Sucrose Diet

The administration of such a transient receptor potential vanilloid 1 (TRPV1) agonist as capsaicin, which is a pungent ingredient of red pepper, promotes energy metabolism and suppresses visceral fat accumulation. We have recently identified monoacylglycerols (MGs) having an unsaturated long-chain fatty acid as the novel TRPV1 agonist in foods. We investigated in this present study the effects of dietary MGs on uncoupling protein 1 (UCP1) expression in interscapular brown adipose tissue (IBAT) and on fat accumulation in mice fed with a high-fat, high-sucrose diet. The MG30 diet that substituted 30% of all lipids for MGs (a mixture of 1-oleoylglycerol, 1-linoleoylglycerol and 1-linolenoylglycerol) significantly increased the UCP1 content of IBAT and decreased the weight of epididymal white adipose tissue, and the serum glucose, total cholesterol and free fatty acid levels. The diet containing only 1-oleoylglycerol as MG also increased UCP1 expression in IBAT. MGs that activated TRPV1 also therefore induced the expression of UCP 1 and prevented visceral fat accumulation as well as capsaicin.     

Influence of red pepper and capsaicin on body composition and lipogenesis in rats

Inclusion of red pepper or its active principle ‘capsaicin’ in the diet led to a lowering of total lipids, particularly triglycerides in the liver. The total body fat was lowered in animals fed red pepper or capsaicin but not in animals fed paprika powder which had negligible capsaicin content. Hyperlipogensis and hypertriglyceridemia caused by fructose feeding were significantly were decreased in capsaicin-fed animals. Activities of the key lipogenic enzymes were reduced as reflected by decreased lipogenesis.     

Stimulation of fecal fat excretion and the disposal of protoporphyrin in a murine model for erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is characterized by toxic accumulation of the hydrophobic compound protoporphyrin (PP). Ferrochelatase-deficient (fch/fch) mice are an animal model for human EPP. Recently, we have demonstrated that the accumulation of another hydrophobic compound, unconjugated bilirubin, could effectively be treated by stimulation of fecal fat excretion. We investigated whether stimulation of fecal fat excretion enhanced the disposal of PP in fch/fch mice. Fch/fch mice were fed for 8 wk with a high-fat diet (16 wt% fat; control) or with the high-fat diet mixed with either a nonabsorbable fat (sucrose polyester) or the intestinal lipase inhibitor orlistat. The effects of the treatments on fecal excretion of fat and PP and on hepatic PP concentrations were compared with control diets. Fecal fat excretion in fch/fch mice on a high-fat diet was higher than in mice on a low-fat diet (+149%, P < 0.05). Sucrose polyesters and orlistat increased fecal fat excretion even more, up to sixfold of control values. However, none of the different treatments affected fecal PP excretion or hepatic PP concentration. Treatment of fch/fch mice with a high-fat diet, a nonabsorbable fat diet, or with orlistat increased the fecal excretion of fat but did not increase fecal PP excretion or decrease hepatic PP concentration. The present data indicate that accumulation of PP is not amenable to stimulation of fecal fat excretion.     

Effect of myostatin depletion on weight gain, hyperglycemia, and hepatic steatosis during five months of high-fat feeding in mice

The marked hypermuscularity in mice with constitutive myostatin deficiency reduces fat accumulation and hyperglycemia induced by high-fat feeding, but it is unclear whether the smaller increase in muscle mass caused by postdevelopmental loss of myostatin activity has beneficial metabolic effects during high-fat feeding. We therefore examined how postdevelopmental myostatin knockout influenced effects of high-fat feeding. Male mice with ubiquitous expression of tamoxifen-inducible Cre recombinase were fed tamoxifen for 2 weeks at 4 months of age. This depleted myostatin in mice with floxed myostatin genes, but not in control mice with normal myostatin genes. Some mice were fed a high-fat diet (60% of energy) for 22 weeks, starting 2 weeks after cessation of tamoxifen feeding. Myostatin depletion increased skeletal muscle mass ～30%. Hypermuscular mice had ～50% less weight gain than control mice over the first 8 weeks of high-fat feeding. During the subsequent 3 months of high-fat feeding, additional weight gain was similar in control and myostatin-deficient mice. After 5 months of high-fat feeding, the mass of epididymal and retroperitoneal fat pads was similar in control and myostatin-deficient mice even though myostatin depletion reduced the weight gain attributable to the high-fat diet (mean weight with high-fat diet minus mean weight with low-fat diet: 19.9 g in control mice, 14.1 g in myostatin-deficient mice). Myostatin depletion did not alter fasting blood glucose levels after 3 or 5 months of high-fat feeding, but reduced glucose levels measured 90 min after intraperitoneal glucose injection. Myostatin depletion also attenuated hepatic steatosis and accumulation of fat in muscle tissue. We conclude that blocking myostatin signaling after maturity can attenuate some of the adverse effects of a high-fat diet.     

Gene-environment interaction: a significant diet-dependent obesity locus demonstrated in a congenic segment on mouse Chromosome 7

We have previously reported suggestive evidence for a locus on Chromosome (Chr) 7 that affects adiposity in F₂ mice from a CAST/Ei × C57BL/6J intercross fed a high-fat diet. Here we characterize the effect of a high-fat (32.6 Kcal% fat) diet on male and female congenic mice with a C57BL/6J background and a CAST/Ei-derived segment on Chr 7. Adiposity index (AI) and weights of certain fat pads were approximately 50% lower in both male and female congenic mice than in control C57BL/6J mice, and carcass fat content was significantly reduced. The reduction of fat depot weights was not seen, however, in congenic animals fed a low-fat chow diet (12 Kcal% fat). The congenic segment is approximately 25 cM in length, extending from D7Mit213 to D7Mit41, and includes the tub, Ucp2, and Ucp3, genes, all of which are candidate genes for this effect. Some polymorphisms have been found on comparing c-DNA sequences of the Ucp2 gene from C57BL/6J and CAST/Ei mice. These results suggest that one or more genes present in the congenic segment modulate the susceptibility to fat deposition on feeding a high-fat diet. We were unable to show any significant difference between the energy intakes of the congenic and the control C57BL/6J mice on the high-fat diet. Also, measurements of energy expenditure in male mice at 6 weeks of age, during the first 2 weeks of exposure to the high-fat diet, failed to show any differences between control and congenic animals. Received: 30 September 1998 / Accepted: 22 December 1998     

TRPV1 agonist monoacylglycerol increases UCP1 content in brown adipose tissue and suppresses accumulation of visceral fat in mice fed a high-fat and high-sucrose diet

The administration of such a transient receptor potential vanilloid 1 (TRPV1) agonist as capsaicin, which is a pungent ingredient of red pepper, promotes energy metabolism and suppresses visceral fat accumulation. We have recently identified monoacylglycerols (MGs) having an unsaturated long-chain fatty acid as the novel TRPV1 agonist in foods. We investigated in this present study the effects of dietary MGs on uncoupling protein 1 (UCP1) expression in interscapular brown adipose tissue (IBAT) and on fat accumulation in mice fed with a high-fat, high-sucrose diet. The MG30 diet that substituted 30% of all lipids for MGs (a mixture of 1-oleoylglycerol, 1-linoleoylglycerol and 1-linolenoylglycerol) significantly increased the UCP1 content of IBAT and decreased the weight of epididymal white adipose tissue, and the serum glucose, total cholesterol and free fatty acid levels. The diet containing only 1-oleoylglycerol as MG also increased UCP1 expression in IBAT. MGs that activated TRPV1 also therefore induced the expression of UCP 1 and prevented visceral fat accumulation as well as capsaicin.     

Lactobacillus gasseri NT Decreased Visceral Fat through Enhancement of Lipid Excretion in Feces of KK-Ay Mice

Dietary supplementation with Lactobacillus gasseri NT significantly decreased visceral fat weight and triglyceride (TG) in the liver in KK-A ^y mice on a high-fat diet, but increased fecal TG. A decrease in lipase activity and down regulation of fatty acid transport proteins in the small intestine was involved in fat accumulation by L. gasseri NT.     

Antiobesity Effects of Bifidobacterium breve Strain B-3 Supplementation in a Mouse Model with High-Fat Diet-Induced Obesity

The aim of the present study was to evaluate the anti-obesity activity of a probiotic bifidobacterial strain in a mouse model with obesity induced by a high-fat diet. The mice were fed a high-fat diet supplemented with Bifidobacterium breve B-3 at 10⁸ or 10⁹ CFU/d for 8 weeks. B. breve B-3 supplementation dose-dependently suppressed the accumulation of body weight and epididymal fat, and improved the serum levels of total cholesterol, fasting glucose and insulin. The bifidobacterial counts in the caecal contents and feces were significantly increased with the B. breve B-3 administration. The expression of genes related to fat metabolism and insulin sensitivity in the gut and epididymal fat tissue was up-regulated by this administration. These results suggest that the use of B. breve B-3 would be effective in reducing the risk of obesity.     

Kefir prevented excess fat accumulation in diet-induced obese mice

Excessive body fat accumulation can result in obesity, which is a serious health concern. Kefir, a probiotic, has recently shown possible health benefits in fighting obesity. This study investigated the inhibitory effects of 0.1 and 0.2% kefir powder on fat accumulation in adipose and liver tissues of high-fat diet (HFD)-induced obese mice. Kefir reduced body weight and epididymal fat pad weight and decreased adipocyte diameters in HFD-induced obese mice. This was supported by decreased expression of genes related to adipogenesis and lipogenesis as well as reduced proinflammatory marker levels in epididymal fat. Along with reduced hepatic triacylglycerol concentrations and serum alanine transaminase and aspartate transaminase activities, genes related to lipogenesis and fatty acid oxidation were downregulated and upregulated, respectively, in liver tissue. Kefir also decreased serum triacylglycerol, total cholesterol, and low-density lipoprotein–cholesterol concentrations. Overall, kefir has the potential to prevent obesity.     

Dietary-induced hypertrophic--hyperplastic obesity in mice

Metabolically intact NMRI mice and genetically obese NZO mice were fed ad lib. either a high-carbohydrate diet (standard) or a high-fat diet for a period of about 11 (NMRI mice) or 38 (NZO mice) wk. In both strains of mice, body weight increased more in the groups fed the high-fat diet. However, caloric intake by NMRI mice fed the high-fat diet was less than that of the controls. In NMRI mice fed the high-fat diet, epididymal and subcutaneous fat cell volumes increased; when these mice were fed the standard diet, only epididymal fat cell volume increased. Epididymal and subcutaneous fat cell numbers increased only in the group fed the high-fat diet. In NMRI mice fed either diet, the postprandial blood glucose was lower in older animals, but plasma insulin remained unchanged. The glucose tolerance deteriorated insignificantly. In NZO mice fed either diet, epididymal fat cell volumes and fat cell numbers increased. In this strain of mice the postprandial blood glucose and plasma insulin exhibited the strain-specific pattern, independent of the diet. In older animals fed either diet the glucose tolerance decreased.     

Antioxidant efficacy of black pepper (Piper nigrum L.) and piperine in rats with high fat diet induced oxidative stress

The present study was aimed to explore the effect of black pepper (Piper nigrum L.) on tissue lipid peroxidation, enzymic and non-enzymic antioxidants in rats fed a high-fat diet. Thirty male Wistar rats (95-115 g) were divided into 5 groups. They were fed standard pellet diet, high-fat diet (20% coconut oil, 2% cholesterol and 0.125% bile salts), high-fat diet plus black pepper (0.25 g or 0.5 g/kg body weight), high-fat diet plus piperine (0.02 g/kg body weight) for a period of 10 weeks. Significantly elevated levels of thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and significantly lowered activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) in the liver, heart, kidney, intestine and aorta were observed in rats fed the high fat diet as compared to the control rats. Simultaneous supplementation with black pepper or piperine lowered TBARS and CD levels and maintained SOD, CAT, GPx, GST, and GSH levels to near those of control rats. The data indicate that supplementation with black pepper or the active principle of black pepper, piperine, can reduce high-fat diet induced oxidative stress to the cells.     

Body Fat Accumulation in Zebrafish Is Induced by a Diet Rich in Fat and Reduced by Supplementation with Green Tea Extract

Fat-rich diets not only induce obesity in humans but also make animals obese. Therefore, animals that accumulate body fat in response to a high-fat diet (especially rodents) are commonly used in obesity research. The effect of dietary fat on body fat accumulation is not fully understood in zebrafish, an excellent model of vertebrate lipid metabolism. Here, we explored the effects of dietary fat and green tea extract, which has anti-obesity properties, on body fat accumulation in zebrafish. Adult zebrafish were allocated to four diet groups and over 6 weeks were fed a high-fat diet containing basal diet plus two types of fat or a low-fat diet containing basal diet plus carbohydrate or protein. Another group of adult zebrafish was fed a high-fat diet with or without 5% green tea extract supplementation. Zebrafish fed the high-fat diets had nearly twice the body fat (visceral, subcutaneous, and total fat) volume and body fat volume ratio (body fat volume/body weight) of those fed low-fat diets. There were no differences in body fat accumulation between the two high-fat groups, nor were there any differences between the two low-fat groups. Adding green tea extract to the high-fat diet significantly suppressed body weight, body fat volume, and body fat volume ratio compared with the same diet lacking green tea extract. 3-Hydroxyacyl-coenzyme A dehydrogenase and citrate synthase activity in the liver and skeletal muscle were significantly higher in fish fed the diet supplemented with green tea extract than in those fed the unsupplemented diet. Our results suggest that a diet rich in fat, instead of protein or carbohydrate, induced body fat accumulation in zebrafish with mechanisms that might be similar to those in mammals. Consequently, zebrafish might serve as a good animal model for research into obesity induced by high-fat diets.     

葛仙米多糖对高脂小鼠血脂和肠道微生物的影响

[目的]研究葛仙米多糖对高脂饲料喂养小鼠血脂和肠道微生物的影响.[方法]将健康的8周龄雄性小鼠分成5组,每组10只:正常组C57/6CNC小鼠(N:灌胃生理盐水,喂饲标准饲料),对照组ApoE-/-小鼠(C:灌胃生理盐水,喂饲标准饲料),模型组ApoE-/-小鼠(M:灌胃生理盐水,喂饲高脂高胆固醇饲料),葛仙米多糖低剂...     

Maternal high-fat diet affects Msi/Notch/Hes signaling in neural stem cells of offspring mice

Numerous research have begun to reveal the importance of maternal nutrition in offspring brain development. Particularly, the maternal obesity or exposure to high-fat diet has been strongly suggested to exert irreversible impact on the structure and function of offspring's brain. However, it remains obscure about whether neonatal neural stem cells (NSCs) in offspring's brain are susceptible to maternal exposure to high-fat diet. Here we focused on the alternation in the Notch signaling in NSCs derived from neonatal mice, which had been given birth by female mice with a high-fat diet and found that, in fact, the high-fat diet administration imposed effects on not only maternal mice, indicated by the accumulation of viscera fat as well as the increase in body weight and serum total cholesterol, but also NSCs in the offspring’s brain, where significant increase was observed in the expression of genes, either downstream of Notch signaling or regulating this pathway, which have been shown essential for the maturation of NSCs. Therefore, our data provided the first evidence for the potential effect of maternal exposure to the high-fat diet on the Notch signaling pathway in offspring’s NSCs, indicating this altered signaling response might contribute to a profound change in offspring’s brains as a result of maternal high-fat diet prior to and during gestation.     

Dietary modulation of circulating leptin levels: site-specific changes in fat deposition and ob mRNA expression.

In order to study the effects of diet on fat distribution, circulating leptin levels and ob mRNA expression, diets of different macronutrient composition were fed to lean mice and gold thioglucose-obese mice. A high-fat diet and 2 high-carbohydrate diets, one containing mostly high-glycaemic-index starch and the other containing low-glycaemic-index starch were fed ad libitum for 10 weeks and were compared to standard laboratory chow. Weight gain was attenuated by feeding low-glycaemic-index starch in all mice and by feeding a high-fat diet in lean mice. Reduced adiposity was seen in lean mice fed low-glycaemic-index starch, whereas increased adiposity was seen in both lean and obese mice fed on the high-fat diet. Circulating leptin levels, when corrected for adiposity, were decreased in all mice fed either the high-fat diet or the low-GI diet. In epididymal fat pads, decreased ob mRNA expression was seen after both high-fat and high-glycaemic-index starch feeding. These results show that diet macronutrient composition contributes to the variability of circulating leptin levels by the combined effects of diet on fat distribution and on site-specific changes in ob mRNA expression.     

Garcinia cambogia Extract Ameliorates Visceral Adiposity in C57BL/6J Mice Fed on a High-Fat Diet

The aim of present study is to evaluate the effects of Garcinia cambogia on the mRNA levels of the various genes involved in adipogenesis, as well as on body weight gain, visceral fat accumulation, and other biochemical markers of obesity in obesity-prone C57BL/6J mice. Consumption of the Garcinia cambogia extract effectively lowered the body weight gain, visceral fat accumulation, blood and hepatic lipid concentrations, and plasma insulin and leptin levels in a high-fat diet (HFD)-induced obesity mouse model. The Garcinia cambogia extract reversed the HFD-induced changes in the expression pattern of such epididymal adipose tissue genes as adipocyte protein aP2 (aP2), sterol regulatory element-binding factor 1c (SREBP1c), peroxisome proliferator-activated receptor γ2 (PPARγ2), and CCAT/enhancer-binding protein α (C/EBPα). These findings suggest that the Garcinia cambogia extract ameliorated HFD-induced obesity, probably by modulating multiple genes associated with adipogenesis, such as aP2, SREBP1c, PPARγ2, and C/EBPα in the visceral fat tissue of mice.     

Betaine supplementation prevents fatty liver induced by a high-fat diet: effects on one-carbon metabolism

The purpose of this study was to examine the effects of betaine supplementation on the regulation of one-carbon metabolism and liver lipid accumulation induced by a high-fat diet in rats. Rats were fed one of three different liquid diets: control diet, high-fat diet and high-fat diet supplemented with betaine. The control and high-fat liquid diets contained, respectively, 35 and 71 % of energy derived from fat. Betaine supplementation involved the addition of 1 % (g/L) to the diet. After three weeks on the high-fat diet the rats had increased total liver fat concentration, liver triglycerides, liver TBARS and plasma TNF-α. The high-fat diet decreased the hepatic S-adenosylmethionine concentration and the S-adenosylmethionine/S-adenosylhomocysteine ratio compared to the control as well as altering the expression of genes involved in one-carbon metabolism. Betaine supplementation substantially increased the hepatic S-adenosylmethionine concentration (~fourfold) and prevented fatty liver and hepatic injury induced by the high-fat diet. It was accompanied by the normalization of the gene expression of BHMT, GNMT and MGAT, which code for key enzymes of one-carbon metabolism related to liver fat accumulation. In conclusion, the regulation of the expression of MGAT by betaine supplementation provides an additional and novel mechanism by which betaine supplementation regulates lipid metabolism and prevents accumulation of fat in the liver.     

Coffee polyphenols suppress diet-induced body fat accumulation by downregulating SREBP-1c and related molecules in C57BL/6J mice

The prevalence of obesity is increasing globally, and obesity is a major risk factor for type 2 diabetes and cardiovascular disease. We investigated the effects of coffee polyphenols (CPP), which are abundant in coffee and consumed worldwide, on diet-induced body fat accumulation. C57BL/6J mice were fed either a control diet, a high-fat diet, or a high-fat diet supplemented with 0.5 to 1.0% CPP for 2-15 wk. Supplementation with CPP significantly reduced body weight gain, abdominal and liver fat accumulation, and infiltration of macrophages into adipose tissues. Energy expenditure evaluated by indirect calorimetry was significantly increased in CPP-fed mice. The mRNA levels of sterol regulatory element-binding protein (SREBP)-1c, acetyl-CoA carboxylase-1 and -2, stearoyl-CoA desaturase-1, and pyruvate dehydrogenase kinase-4 in the liver were significantly lower in CPP-fed mice than in high-fat control mice. Similarly, CPP suppressed the expression of these molecules in Hepa 1-6 cells, concomitant with an increase in microRNA-122. Structure-activity relationship studies of nine quinic acid derivatives isolated from CPP in Hepa 1-6 cells suggested that mono- or di-caffeoyl quinic acids (CQA) are active substances in the beneficial effects of CPP. Furthermore, CPP and 5-CQA decreased the nuclear active form of SREBP-1, acetyl-CoA carboxylase activity, and cellular malonyl-CoA levels. These findings indicate that CPP enhances energy metabolism and reduces lipogenesis by downregulating SREBP-1c and related molecules, which leads to the suppression of body fat accumulation.     

Effects of Excess Energy Intake on Glucose and Lipid Metabolism in C57BL/6 Mice

Excess energy intake correlates with the development of metabolic disorders. However, different energy-dense foods have different effects on metabolism. To compare the effects of a high-fat diet, a high-fructose diet and a combination high-fat/high-fructose diet on glucose and lipid metabolism, male C57BL/6 mice were fed with one of four different diets for 3 months: standard chow; standard diet and access to fructose water; a high fat diet; and a high fat diet with fructose water. After 3 months of feeding, the high-fat and the combined high-fat/high-fructose groups showed significantly increased body weights, accompanied by hyperglycemia and insulin resistance; however, the high-fructose group was not different from the control group. All three energy-dense groups showed significantly higher visceral fat weights, total cholesterol concentrations, and low-density lipoprotein cholesterol concentrations compared with the control group. Assays of basal metabolism showed that the respiratory quotient of the high-fat, the high-fructose, and the high-fat/high-fructose groups decreased compared with the control group. The present study confirmed the deleterious effect of high energy diets on body weight and metabolism, but suggested that the energy efficiency of the high-fructose diet was much lower than that of the high-fat diet. In addition, fructose supplementation did not worsen the detrimental effects of high-fat feeding alone on metabolism in C57BL/6 mice.     

有氧运动对高脂饮食小鼠肝脏中CLK2蛋白表达的影响

目的: 探讨有氧运动对高脂饮食小鼠肝脏中Cdc2 激酶(CLK2)蛋白表达及肝脏脂肪含量的影响。方法: 雄性C57/BL6小鼠经正常饮食或高脂饮食16周后,分为正常饮食组、高脂饮食组和高脂饮食+运动组(8周有氧运动),每组10只小鼠。采用免疫印迹方法比较各组小鼠肝脏CLK2蛋白表达;采用油红O染色法比较各组小鼠肝脏脂肪含量;采用实时定量PCR方法比较各组小鼠脂肪代谢相关基因。结果:与正常饮食组小鼠相比,高脂饮食小鼠表现出胰岛素抵抗,肝脏CLK2蛋白含量增加,以及肝脏脂肪积累增加。然而有氧运动可改善高脂饮食小鼠胰岛素抵抗状态,并抑制肝脏中CLK2蛋白增加。结论:有氧运动可降低高脂饮食小鼠肝脏中CLK2蛋白表达,而改善肥胖小鼠肝脏脂肪堆积及代谢紊乱。