高糖饮食导致大鼠肝脏脂代谢紊乱实验研究

目的 探讨高糖饮食对大鼠肝脏过氧化物酶体脂肪酸B-氧化的影响.方法 用高糖饮食饲养大鼠24周,观察体重,血清总胆固醇(TC)、三酰甘油(TG)、游离脂肪酸(FFA),肝脏过氧化氢酶、脂酰CoA氧化酶和过氧化物酶体脂肪酸β-氧化活性的变化.结果 试验组TG、T℃、FFA与对照组相比有不同程度升高(P<0.01).试验组大...     

The herbal composition GGEx18 from Laminaria japonica,Rheum palmatum,and Ephedra sinica inhibits high-fat diet-induced hepatic steatosis via hepatic PPARα activation

Context: The activation of peroxisome proliferator-activated receptor α (PPARα) target genes promotes hepatic oxidation of fatty acids. We hypothesized that Gyeongshingangjeehwan 18 (GGEx18), a mixture of three herbs, Laminaria japonica Aresch (Laminariaceae), Rheum palmatum L. (Polygonaceae), and Ephedra sinica Stapf (Ephedraceae), can regulate high-fat diet-induced hepatic steatosis through PPARα activation in the liver.

Objective: To investigate the effects of GGEx18 on obesity-related hepatic steatosis and the responsible mechanism.

Materials and methods: The effects of GGEx18 on hepatic lipid accumulation, serum lipid profiles, and the expression of PPARα target genes were studied in high-fat diet-induced obese mice. The effects of GGEx18 on the expression of the PPARα targets and PPARα reporter gene activation were measured in NMu2Li liver cells.

Results: GGEx18 administration to obese mice for 9 weeks markedly (p?<?0.05) decreased hepatic lipid accumulation compared with that in obese control mice. Serum triglyceride and total cholesterol levels were significantly (p <0.05) decreased by GGEx18. GGEx18 treatment increased the messenger RNA levels of PPARα target genes, which are responsible for fatty acid oxidation, in liver tissues. Consistent with the in vivo data, similar activation of genes was observed in GGEx18-treated NMu2Li liver cells. GGEx18 also elevated PPARα reporter gene expression in NMu2Li cells.

Discussion and conclusion: These results suggest that GGEx18 prevents hepatic steatosis and hyperlipidemia in high-fat diet-induced obese mice, and this process may be mediated through PPARα activation in the liver.     

Beneficial effects of Undaria pinnatifida ethanol extract on diet-induced-insulin resistance in C57BL/6J mice

This study was performed to evaluate the beneficial effect of Undaria pinnatifida ethanol extract (UEFx) on insulin resistance in diet-induced obese mice. A high-fat diet was supplemented with the UEFx at 0.69% (wt/wt) dose, which contains an equivalent amount of 0.02% fucoxanthin (wt/wt), or with Fx at 0.02% (wt/wt) dose in diet. After 9 weeks, both UEFx supplement significantly lowered the amount of visceral fat, the size of adipocyte, the fasting blood glucose concentration, the plasma insulin and the insulin resistance index similar to pure as shown by Fx supplement, compared to the high-fat (HF) control group. Blood glucose level was negatively correlated with hepatic glucokinase activity (r = −0.533, p < 0.05), whereas positively correlated with hepatic gluconeogenic enzyme activities (r = 0.463, p < 0.05 for glucose-6-phosphatase; r = 0.457, p < 0.05 for phosphoenolpyruvate carboxykinase). Ratio of hepatic glucokinase/glucose-6-phosphatase and glycogen content were significantly elevated by the UEFx and Fx supplements. Supplementation of the UEFx as well as Fx seemed to stimulate the β-oxidation activity and inhibit the phosphatidate phosphohydrolase activity resulting in a decrease in the hepatic lipid droplet accumulation. The results indicate that the UEFx can prevent insulin resistance and hepatic fat accumulation that is partly mediated by modulating the hepatic glucose and lipid homeostasis in the high fat-induced obese mice.     

The herbal composition GGEx18 from Laminaria japonica, Rheum palmatum, and Ephedra sinica inhibits high-fat diet-induced hepatic steatosis via hepatic PPARα activation

Context: The activation of peroxisome proliferator-activated receptor α (PPARα) target genes promotes hepatic oxidation of fatty acids. We hypothesized that Gyeongshingangjeehwan 18 (GGEx18), a mixture of three herbs, Laminaria japonica Aresch (Laminariaceae), Rheum palmatum L. (Polygonaceae), and Ephedra sinica Stapf (Ephedraceae), can regulate high-fat diet-induced hepatic steatosis through PPARα activation in the liver. Objective: To investigate the effects of GGEx18 on obesity-related hepatic steatosis and the responsible mechanism. Materials and methods: The effects of GGEx18 on hepatic lipid accumulation, serum lipid profiles, and the expression of PPARα target genes were studied in high-fat diet-induced obese mice. The effects of GGEx18 on the expression of the PPARα targets and PPARα reporter gene activation were measured in NMu2Li liver cells. Results: GGEx18 administration to obese mice for 9 weeks markedly (p?相似文献   

Chlorogenic acid exhibits anti-obesity property and improves lipid metabolism in high-fat diet-induced-obese mice

This study investigated the efficacy of chlorogenic acid on altering body fat in high-fat diet (37% calories from fat) induced-obese mice compared to caffeic acid. Caffeic acid or chlorogenic acid was supplemented with high-fat diet at 0.02% (wt/wt) dose. Both caffeic acid and chlorogenic acid significantly lowered body weight, visceral fat mass and plasma leptin and insulin levels compared to the high-fat control group. They also lowered triglyceride (in plasma, liver and heart) and cholesterol (in plasma, adipose tissue and heart) concentrations. Triglyceride content in adipose tissue was significantly lowered, whereas the plasma adiponectin level was elevated by chlorogenic acid supplementation compared to the high-fat control group. Body weight was significantly correlated with plasma leptin (r = 0.894, p < 0.01) and insulin (r = 0.496, p < 0.01) levels, respectively. Caffeic acid and chlorogenic acid significantly inhibited fatty acid synthase, 3-hydroxy-3-methylglutaryl CoA reductase and acyl-CoA:cholesterol acyltransferase activities, while they increased fatty acid β-oxidation activity and peroxisome proliferator-activated receptors α expression in the liver compared to the high-fat group. These results suggest that caffeic acid and chlorogenic acid improve body weight, lipid metabolism and obesity-related hormones levels in high-fat fed mice. Chlorogenic acid seemed to be more potent for body weight reduction and regulation of lipid metabolism than caffeic acid.     

Berberine ameliorates renal interstitial inflammation and fibrosis in mice with unilateral ureteral obstruction

Berberine acts via multiple pathways to alleviate fibrosis in various tissues and shows renoprotective effects. However, its role and underlying mechanisms in renal fibrosis remain unclear. Herein, we aimed to investigate the protective effects and molecular mechanisms of berberine against unilateral ureteric obstruction-induced renal fibrosis. The results indicated that berberine treatment (50 mg/kg/day) markedly alleviated histopathological alterations, collagen deposition and inflammatory cell infiltration in kidney tissue and restored mouse renal function. Mechanistically, berberine intervention inhibited NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation and the levels of the inflammatory cytokine IL-1β in the kidneys of unilateral ureteric obstruction mice. In addition, berberine relieved unilateral ureteric obstruction-induced renal injury by activating adenosine monophosphate-activated protein kinase (AMPK) signalling and promoting fatty acid β-oxidation. In vitro models showed that berberine treatment prevented the TGF-β1-induced profibrotic phenotype of hexokinase 2 (HK-2) cells, characterized by loss of an epithelial phenotype (alpha smooth muscle actin [α-SMA]) and acquisition of mesenchymal marker expression (E-cadherin), by restoring abnormal fatty acid β-oxidation and upregulating the expression of the fatty acid β-oxidation related-key enzymes or regulators (phosphorylated-AMPK, peroxisome proliferator activated receptor alpha [PPARα] and carnitine palmitoyltransferase 1A [CPT1A]). Collectively, berberine alleviated renal fibrosis by inhibiting NLRP3 inflammasome activation and protected tubular epithelial cells by reversing defective fatty acid β-oxidation. Our findings might be exploited clinically to provide a potential novel therapeutic strategy for renal fibrosis.     

Ameliorating effects of casein glycomacropeptide on obesity induced by high-fat diet in male Sprague-Dawley rats

The effect of casein glycomacropeptide (GMP) as a specific regulating mediator in obese rats induced by high-fat (HF) diet was investigated. Male obese Sprague-Dawley (SD) rats induced by high-fat diet for 8 weeks period were fed high-fat, high-fat with GMP of 100 mg/kg BW (HFLG), 200 mg/kg BW (HFMG) and 400 mg/kg BW (HFHG) for 6 weeks. Compared with the high-fat control (HFC) group GMP supplementation significantly decreased adipose tissue weight, activity of fatty acid synthase (FAS) and glycerol-3-phosphate dehydrogenase (GPDH). Hepatic lipid droplet size, plasma and hepatic lipid levels markedly reduced. Moreover, GMP reduces plasma total cholesterol and low-density lipoprotein (LDL) cholesterol as well as hepatic-cholesterol and triglycerides. The liver steatosis observed in obese rats was also prevented by GMP supplement. In addition, GMP significantly diminished mitochondrial and liver malondialdehyde (MDA) production, and obviously elevated the activities of mitochondrial and hepatic superoxidase dismutase (SOD) and glutathione peroxidase (GSH-Px). Leptin production and proinflammatory cytokines such as TNF-α and IL-6 secretion decreased. Taken together, GMP can reduce lipid accumulation and enhance antioxidant capability of obese rats. It suggests that GMP can counteract high-fat diet-induced obesity, which might make it a potential ingredient with anti-obesity activity.     

Hepatic effects of a methionine-choline-deficient diet in hepatocyte RXRα-null mice

Retinoid X receptor-α (RXRα) is an obligate partner for several nuclear hormone receptors that regulate important physiological processes in the liver. In this study the impact of hepatocyte RXRα deficiency on methionine and choline deficient (MCD) diet-induced steatosis, oxidative stress, inflammation, and hepatic transporters gene expression were examined. The mRNA of sterol regulatory element-binding protein (SREBP)-regulated genes, important for lipid synthesis, were not altered in wild type (WT) mice, but were increased 2.0- to 5.4-fold in hepatocyte RXRα-null (H-RXRα-null) mice fed a MCD diet for 14 days. Furthermore, hepatic mRNAs and proteins essential for fatty acid β-oxidation were not altered in WT mice, but were decreased in the MCD diet-fed H-RXRα-null mice, resulting in increased hepatic free fatty acid levels. Cyp2e1 enzyme activity and lipid peroxide levels were induced only in MCD-fed WT mice. In contrast, hepatic mRNA levels of pro-inflammatory factors were increased only in H-RXRα-null mice fed the MCD diet. Hepatic uptake transporters Oatp1a1 and Oatp1b2 mRNA levels were decreased in WT mice fed the MCD diet, whereas the efflux transporter Mrp4 was increased. However, in the H-RXRα-null mice, the MCD diet only moderately decreased Oatp1a1 and induced both Oatp1a4 and Mrp4 gene expression. Whereas the MCD diet increased serum bile acid levels and alkaline phosphatase activity in both WT and H-RXRα-null mice, serum ALT levels were induced (2.9-fold) only in the H-RXRα-null mice. In conclusion, these data suggest a critical role for RXRα in hepatic fatty acid homeostasis and protection against MCD-induced hepatocyte injury.     

Ezetimibe improves high fat and cholesterol diet-induced non-alcoholic fatty liver disease in mice

Ezetimibe is a novel cholesterol and plant sterol absorption inhibitor that reduces plasma low-density lipoprotein-cholesterol by selectively binding to the intestinal cholesterol transporter, Niemann-Pick C1-Like 1. Mice deficient in Niemann-Pick C1-Like 1 are protected from high fat/cholesterol diet-induced fatty liver as well as hypercholesterolemia. The object of the present study was to determine whether ezetimibe treatment could reduce hepatic steatosis in diet-induced obese mice. C57BL/6J mice were fed a high fat/cholesterol containing semi-purified diet (45% Kcal fat and 0.12% cholesterol) for 7 months after weaning. These mice were not only obese, but also developed hepatomegaly and hepatic steatosis, with varying degrees of liver fibrosis and steatohepatitis. About 87% of the mice on the high fat/cholesterol diet for 7 months had elevated plasma alanine aminotransferase activity, a biomarker for non-alcoholic fatty liver disease. Chronic administration of ezetimibe for 4 weeks significantly reduced hepatomegaly by decreasing hepatic triglyceride, cholesteryl ester and free cholesterol in diet-induced obese mice fed high fat/cholesterol diet for 7 months. Chronic ezetimibe treatment also significantly decreased plasma alanine aminotransferase activity. These results suggest that ezetimibe may be a novel treatment for high fat/cholesterol-induced non-alcoholic fatty liver disease.     

Protective potentials of wild rice (Zizania latifolia (Griseb) Turcz) against obesity and lipotoxicity induced by a high-fat/cholesterol diet in rats

The study evaluates the protective potentials of wild rice against obesity and lipotoxicity induced by a high-fat/cholesterol diet in rats. In addition to the rats of low-fat diet group, others animals were exposed to a high-fat/cholesterol diet condition for 8 weeks. The city diet (CD) is based on the diet consumed by urban residents in modern China, which is rich in fat/cholesterol and high in carbohydrates from white rice and processed wheat starch. The chief source of dietary carbohydrates of wild rice diet (WRD) is from Chinese wild rice and other compositions are the same with CD. Rats fed CD showed elevated body and liver organ weights, lipid profiles, free fatty acids (FFA) and leptin comparable with rats fed high-fat/cholesterol diet (HFD) known to induce obesity and hyperlipidaemia in this species. However, rats consuming WRD suppressed the increase of lipid droplets accumulation, FFA, and leptin, and the decrease of lipoprotein lipase and adipose triglyceride lipase. Meanwhile, WRD prevented high-fat/cholesterol diet-induced elevation in protein expression of sterol-regulatory element binding protein-1c, and gene expression of fatty acid synthase and acetyl-CoA carboxylase. These findings indicate that wild rice as a natural food has the potentials of preventing obesity and liver lipotoxicity induced by a high-fat/cholesterol diet in rats.     

Inhibition of hepatic carnitine palmitoyl-transferase I (CPT IA) by valproyl-CoA as a possible mechanism of valproate-induced steatosis

Background/Aims

Carnitine palmitoyl-transferase I (CPT I) catalyses the synthesis of long-chain (LC)-acylcarnitines from LC-acyl-CoA esters. It is the rate-limiting enzyme of mitochondrial fatty acid β-oxidation (FAO) pathway and its activity is regulated by malonyl-CoA. The antiepileptic drug valproic acid (VPA) is a branched chain fatty acid that is activated to the respective CoA ester in the intra- and extra-mitochondrial compartments. This drug has been associated with a clear inhibition of mitochondrial FAO, which motivated our study on its potential effect on hepatic CPT I.

Methods

To investigate the effect of valproyl-CoA (VP-CoA) on CPT I, we performed in vitro studies using control human fibroblasts and rat CPT IA expressed in Saccharomyces cerevisiae. In addition to the wild-type enzyme, two mutant rCPT IAs were studied, one of which showing increased sensitivity towards malonyl-CoA (S24A/Q30A), whereas the other one is insensitive to malonyl-CoA (E3A).

Results

We demonstrate that VP-CoA inhibits the CPT I activity in control fibroblasts. Similar results were obtained using rCPT IA WT and S24A/Q30A. Importantly, VP-CoA also inhibited the activity of the rCPT IA E3A. We show that VP-CoA inhibits CPT IA competitively with respect to palmitoyl-CoA, and non-competitively to carnitine. Evidence is provided that VP-CoA interferes at the catalytic domain of CPT IA affecting the sensitivity for malonyl-CoA.

Conclusions

The interference of VP-CoA with CPT IA, a pivotal enzyme in mitochondrial fatty acid β-oxidation, may be a crucial mechanism in the drug-induced hepatotoxicity and the weight gain frequently observed in patients under VPA therapy.     

G protein-coupled receptor 35 attenuates nonalcoholic steatohepatitis by reprogramming cholesterol homeostasis in hepatocytes

Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease worldwide.Fat accumulation "sensitizes" the liver to insult and leads to nonalcoholic steatohepatitis(NASH).G protein-coupled receptor 35(GPR35) is involved in metabolic stresses,but its role in NAFLD is unknown.We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis.Specifically,we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose(HFC...     

Bifendate treatment attenuates hepatic steatosis in cholesterol/bile salt- and high-fat diet-induced hypercholesterolemia in mice

Effects of bifendate, a synthetic intermediate of schisandrin C (a dibenzocyclooctadiene derivative), on liver lipid contents were investigated in experimentally-induced hypercholesterolemia in mice. Hypercholesterolemia was induced by either chronic administration of cholesterol/bile salt or feeding a high-fat diet containing cholesterol and/or bile salt. Hepatic and serum total cholesterol levels were significantly increased (42-268% and 23-124%, respectively) in cholesterol or high-fat diet-treated mice, when compared with control animals receiving vehicle or normal diet. Hepatic triglyceride level was increased (up to 108%), but serum triglyceride level was significantly reduced by 23-63% in hypercholesterolemic mice. Daily administration of bifendate (0.03-1.0 g/kg, i.g.) for 4 days decreased hepatic levels of total cholesterol (9-37%) and triglyceride (10-37%) in hypercholesterolemic mice. Supplementing the high-fat diet with bifendate (0.25%, w/w) caused decreases in hepatic total cholesterol (25-56%) and triglyceride (22-44%) levels following 7 or 14 days of experiment, respectively, when compared with animals fed with high-fat diet not supplemented with bifendate. While fenofibrate treatment decreased both hepatic and serum lipid levels in hypercholesterolemic mice, bifendate treatment did not reduce serum lipid levels. Bifendate and fenofibrate caused an increase (10-41% and 59-98%, respectively) in hepatic index of hypercholesterolemic mice. The results indicate that bifendate treatment can invariably decrease hepatic (but not serum) lipid levels in various mouse models of hypercholesterolemia.     

Food preservative sorbic acid deregulates hepatic fatty acid metabolism

Sorbic acid (SA) is one of the most commonly used food preservatives worldwide. Despite SA having no hepatotoxicity at legal dosages, its effect on hepatic lipid metabolism is still unclear. We investigated the effect of SA on hepatic lipid metabolism and its mechanism of action in C57BL/6 mice. Daily treatment with SA (1 g/kg in diet) for 4 weeks did not alter the body weight, organ weight, and blood lipids in mice. However, hepatic lipid accumulation, particularly that of triglycerides, fatty acids, and glycerol, but not cholesteryl ester and free cholesterol, was increased with SA treatment. Mechanistically, SA decreased the expression of proteins related to de novo fatty acid lipogenesis, fatty acid internalization, and very low-density lipoprotein (VLDL) secretion-related pathways, including sterol regulatory element-binding proteins, acetyl-coA carboxylase, fatty acid synthase, liver fatty acid-binding protein, CD36, and apolipoprotein E. In contrast, SA increased the expression of diacylglycerol O-acyltransferase 2, the key enzyme for triacylglycerol synthesis. Moreover, SA downregulated the protein expression of autophagy-related and β-oxidation-related pathways, the two major metabolic pathways for lipid metabolism, including LC-3, beclin-1, autophagy related protein 5 (ATG-5) and ATG-7, acyl-CoA synthetase long chain family member 1, carnitine palmitoyltransferase Iα, peroxisome proliferator-activated receptor α (PPARα), PPARγ, and PPARγ coactivator-1. Collectively, SA deregulates de novo lipogenesis and fatty acid internalization, VLDL secretion, autophagy, and β-oxidation in the liver, leading to impaired lipid clearance and ultimately, resulting in lipid accumulation in the liver.     

Ferulic acid improves lipid and glucose homeostasis in high‐fat diet‐induced obese mice

Ferulic acid (FA) is a plant phenolic acid that has several pharmacological effects including antihyperglycaemic activity. Thus, the objective of this study is to investigate the effect of FA on glucose and lipid metabolism in high‐fat diet (HFD)‐induced obese mice. Institute for Cancer Research (ICR) mice were fed a HFD (45 kcal% fat) for 16 weeks. At the ninth week of induction, the obese mice were orally administered with daily FA doses of 25 and 50 mg/kg for the next eight weeks. The results show that FA significantly reduced the elevated blood glucose and serum leptin levels, lowered the insulin resistance, and increased the serum adiponectin level. Moreover, serum lipid level, and liver cholesterol and triglyceride accumulations were also reduced. The histological examination showed clear evidence of a decrease in the lipid droplets in liver tissues and smaller size of fat cells in the adipose tissue in the obese mice treated with FA. Interestingly, FA reduced the expression of hepatic lipogenic genes such as sterol regulatory element‐binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl‐CoA carboxylase (ACC). It could also up‐regulate hepatic carnitine palmitoyltransferase 1a (CPT1a) gene and peroxisome proliferator‐activated receptor alpha (PPARα) proteins. The FA treatment was also found to suppress the protein expressions of hepatic gluconeogenic enzymes, phosphoenolpyruvate carboxylase (PEPCK) and glucose‐6‐phosphatase (G6Pase). In conclusion, the findings of this study demonstrate that FA improves the glucose and lipid homeostasis in HFD‐induced obese mice probably via modulating the expression of lipogenic and gluconeogenic genes in liver tissues.     

Supplementation of whole persimmon leaf improves lipid profiles and suppresses body weight gain in rats fed high-fat diet.

The objective of this study was to investigate the hypolipidemic effects of powdered whole persimmon leaf supplement in rats fed high-fat diet. Three groups of male Sprague-Dawley rats during 6 weeks were fed different diet: normal control (NC), high-fat (HF), and high-fat supplemented with powdered whole persimmon leaf (PL; 5%, wt/wt) groups. Body weight and relative weight of interscapular brown adipose tissue were significantly lower in the PL group than in the HF group, while plasma leptin concentration was higher. The supplementation of persimmon leaf significantly lowered the plasma total cholesterol and triglyceride concentrations, whereas elevated the ratio of HDL-C/total-C and improved the atherogenic index. Persimmon leaf supplementation led the hepatic cholesterol and triglyceride values to similar levels to the NC group. Accumulation of hepatic lipid droplets and the epididymal white adipocyte size of PL group were diminished comparing to the HF group. Hepatic HMG-CoA and ACAT activities were significantly higher in the PL group than in other groups. Contents of fecal triglyceride, cholesterol and acidic sterol were significantly higher in the PL group than in the HF group. Accordingly, we suggest that supplementation of the powdered whole persimmon leaf improves plasma and hepatic lipid levels profile partly via the increased fecal lipids in high-fat fed rats. These beneficial effects may be due to the properties of its phenolic compounds (1.15 g/100g) and high fiber (63.48 g/100g) content in the powdered persimmon leaf.     

Role of human pregnane X receptor in high fat diet-induced obesity in pre-menopausal female mice

Obesity is a complex metabolic disorder that is more prevalent among women. Until now, the only relevant rodent models of diet-induced obesity were via the use of ovariectomized (“postmenopausal”) females. However, recent reports suggest that the xenobiotic nuclear receptor pregnane X receptor (PXR) may contribute to obesity. Therefore, we compared the roles of mouse and human PXRs in diet-induced obesity between wild type (WT) and PXR-humanized (hPXR) transgenic female mice fed either control or high-fat diets (HFD) for 16 weeks. HFD-fed hPXR mice gained weight more rapidly than controls, exhibited hyperinsulinemia, and impaired glucose tolerance. Fundamental differences were observed between control-fed hPXR and WT females: hPXR mice possessed reduced estrogen receptor α (ERα) but enhanced uncoupling protein 1 (UCP1) protein expression in white adipose tissue (WAT); increased protein expression of the hepatic cytochrome P450 3A11 (CYP3A11) and key gluconeogenic enzymes phosphoenolpyruvate carboxykinase and glucose 6-phosphatase, and increased total cholesterol. Interestingly, HFD ingestion induced both UCP1 and glucokinase protein expression in WT mice, but inhibited these enzymes in hPXR females. Unlike WT mice, CYP3A11 protein, serum 17β-estradiol levels, and WAT ERα expression were unaffected by HFD in hPXR females. Together, these studies indicate that the hPXR gene promotes obesity and metabolic syndrome by dysregulating lipid and glucose homeostasis while inhibiting UCP1 expression. Furthermore, our studies indicate that the human PXR suppresses the protective role of estrogen in metabolic disorders. Finally, these data identify PXR-humanized mice as a promising in vivo research model for studying obesity and diabetes in women.     

Immature Citrus sunki peel extract exhibits antiobesity effects by β-oxidation and lipolysis in high-fat diet-induced obese mice

The peel of Citrus sunki HORT. ex TANAKA has been widely used in traditional Asian medicine for the treatment of many diseases, including indigestion and bronchial asthma. In this study, we investigated the antiobesity activity of immature C. sunki peel extract (designated CSE) using high-fat diet (HFD)-induced obese C57BL/6 mice and mature 3T3-L1 adipocytes. In the animal study, body weight gain, adipose tissue weight, serum total cholesterol, and triglyceride in the CSE-administered group decreased significantly compared to the HFD group. Also, CSE supplementation reduced serum levels of glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and lactate dehydrogenase. Moreover, it significantly decreased the accumulation of fatty droplets in liver tissue, suggesting a protective effect against HFD-induced hepatic steatosis. Dietary supplementation with CSE reversed the HFD-induced decrease in the phosphorylation levels of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), which are related to fatty acid β-oxidation, in the epididymal adipose tissue. Also, CSE increased AMPK and ACC phosphorylation in mature 3T3-L1 adipocytes. CSE also enhanced lipolysis by phosphorylation of cAMP-dependent protein kinase (PKA) and hormone-sensitive lipase (HSL) in mature 3T3-L1 adipocytes. These results suggest that CSE had an antiobesity effect via elevated β-oxidation and lipolysis in adipose tissue.     

Bicyclol, a synthetic dibenzocyclooctadiene derivative, decreases hepatic lipids but increases serum triglyceride level in normal and hypercholesterolaemic mice

Bicyclol is used for the treatment of chronic hepatitis B in China. In this study, the effects of bicyclol (100 or 300 mg kg(-1), p.o.) on serum and liver lipid contents were investigated in both normal and experimentally induced hypercholesterolaemic mice. Hypercholesterolaemia was induced by either oral administration of cholesterol/bile salt or feeding a diet containing lard/cholesterol. Daily administration of bicyclol for 7 days dose-dependently increased the serum triglyceride level (29-80%) but slightly decreased the hepatic total cholesterol level (12-17%) in normal mice. Co-administration of bicyclol with cholesterol/bile salt decreased the hepatic triglyceride and total cholesterol levels (7-15% and 25-31%, respectively), when compared with the drug-untreated and cholesterol/bile salt-treated group. Bicyclol treatment for 7 days decreased hepatic triglyceride (5-76%) and total cholesterol (5-48%) levels in mice fed with high-fat/cholesterol diet. In contrast, bicyclol treatment increased the serum triglyceride level (18-77%) in mice treated with cholesterol/bile salt or fed with high-fat/cholesterol diet. Bicyclol treatment also caused an increase in hepatic index of normal and hypercholesterolaemic mice (3-32%). The results indicate that bicyclol treatment can invariably decrease hepatic lipid levels and increase serum triglyceride levels in normal and hypercholesterolaemic mice.