A novel berberine‐metformin hybrid compound exerts therapeutic effects on obese type 2 diabetic rats

In this study, we investigated the biological activities of a novel berberine‐metformin hybrid compound (BMH473) as an anti‐diabetic agent. BMH473 exhibited significant anti‐hyperglycaemic and anti‐hyperlipidaemic effects on T2DM rats. In white adipose tissue, BMH473 reduced the perirenal and epididymal adipose tissue mass and modulated the lesions in perirenal adipose tissue, by inhibiting the protein expressions of PPAR‐?, C/EBP‐α and SREBP‐1c as well as the mRNA expressions of lipogenic genes. Moreover, BMH473 downregulated the levels of pro‐inflammatory cytokines in perirenal adipose tissue through the suppression of p‐NF‐κB. In liver, BMH473 reduced liver ectopic fat accumulation, by regulating the protein expression levels of SREBP‐1c and PPAR‐α as well as the mRNA expression levels of lipogenic genes. In addition, BMH473 inhibited hepatic gluconeogenesis by promoting the phosphorylation levels of AMPK α and ACC, and down‐regulating the mRNA expression levels of FBPase, G6Pase and PEPCK. Furthermore, BMH473 exhibited significant inhibitory effects on lipogenesis and lipid accumulation in 3T3‐L1 adipocytes by modulating the protein expression levels of PPAR‐?, C/EBP‐α and SREBP‐1 c as well as the mRNA expression levels of lipogenic genes. In conclusion, our results suggest that the newly synthesized BMH473 is beneficial for maintaining glucose and lipid homeostasis in type 2 diabetic rats, and exhibits better anti‐hyperlipidaemic effects compared to metformin and berberine.     

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.     

Inhibition of stearoyl-CoA desaturase1 activates AMPK and exhibits beneficial lipid metabolic effects in vitro

Stearoyl-CoA desaturase1 (SCD1) whole body deficiency protects mice from diet-induced obesity. However the specific mechanism of how SCD1 deficiency protects mice from obesity is not clear yet. To understand the tissue-specific role of SCD1 in energy homeostasis, we investigated the responses of adipocytes, hepatocytes and myotubes to SCD1 inhibition. 3T3-L1 adipocytes treated with a SCD1 inhibitor had decreased expression of lipogenic genes including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and sterol-regulatory element binding protein 1c (SREBP1c) while the expression of fatty acid oxidative genes including carnitine palmitoyltransferase 1 (CPT1), uncoupling protein 2 (UCP2), and peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1-α) remained unaltered. In mouse primary hepatocytes, treatment with the inhibitor reduced the expression of FAS, ACC, and SREBP1c but increased the expression of fatty acid oxidative genes including acyl-CoA oxidase (AOX), CPT1, and PGC1-α. In addition, inhibitor-treated C2C12 myotubes showed decrease in ACC and FAS expression and increase in expression of CPT1, AOX and PGC1-α. AMP-activated protein kinase (AMPK) is known to regulate cellular metabolism in response to available energy and AMPK activation is associated with enhancement of fatty acid oxidation and suppression of lipogenesis. In all tested cell models, AMPK phosphorylation was increased significantly when SCD1 was inhibited. Taken together, our results indicate that inhibition of SCD1 activity has beneficial lipid metabolic effects of decreased lipogenesis and/or increased fatty acid oxidation, which is at least in part due to an increase of AMPK activation.     

五味子-甘草配伍的含药血清对肝细胞脂质堆积的影响及机制研究

目的研究大剂量五味子配伍甘草后对肝细胞脂质堆积的干预作用,并探讨相关机制。方法 SD大鼠给予五味子(SF,五味子生药量为3.9 g·kg-1的醇提物)、五味子-甘草(SG,1∶1,1∶1.5,3.9 g·kg-1),1次/d,连续给药7 d后制备含药血清。基于L02细胞,分对照组(C)、SF、SG(1∶1)和(1∶1.5)组,作用48 h后,检测LDH释放量、细胞内TG、TC含量;RT-PCR法检测PPAR-α、PPAR-γ、Fabp1/2、SREBP1c、ACCα、FAS的mRNA表达。结果与C组比,SF升高TG、TC含量,降低PPAR-α、PPAR-γ的mRNA表达,升高SREBP1c、ACCα的mRNA表达;与SF比,SG(1∶1)降低TG、TC含量,降低Fabp1/2、FAS的mRNA表达,升高SREBP1c的mRNA表达;SG(1∶1.5)仅降低TC含量,升高PPAR-γ、SREBP1c的mRNA表达,降低Fabp1/2、FAS的mRNA表达。结论五味子含药血清可显著升高肝细胞中TG、TC含量,配伍甘草可降低其升高的TG、TC含量,降低脂质堆积,其机制可能与调控PPAR-α、PPAR-γ、Fabp1/2、SREBP1c、ACCα、FAS基因mRNA的表达有关。     

Taurine prevents high‐fat diet‐induced‐hepatic steatosis in rats by direct inhibition of hepatic sterol regulatory element‐binding proteins and activation of AMPK

This study investigated if the protective effect of taurine against high fat diet‐induced hepatic steatosis involves modulating the hepatic activity of 5' AMP‐activated protein kinase (AMPK) and levels/activity of the sterol regulatory element‐binding proteins‐1/2 (SREBP1/2). Rats were divided into four groups (n = 12/group) as (a) STD, fed standard diet (3.85 kcal/g); (b) STD + taurine (500 mg/kg); (c) HFD, fed HFD (4.73 kcal/g); and (d) HFD + taurine. All treatments were conducted for 12 weeks. Independent of food intake or modulating glucose or insulin levels, taurine administration to STD and HFD‐fed rats significantly lowered weekly weight gain and the accumulation of the retroperitoneal, visceral and subcutaneous fats. In both groups, taurine also reduced serum and hepatic levels of triglycerides and cholesterol and reduced hepatic mRNA and protein levels of fatty acid synthase (FAS), acetyl CoA carboxylase‐1 (ACC‐1), HMG‐CoA‐reductase and HMG‐CoA synthetase. In control rats only, taurine reduced hepatic levels of mature forms of sterol regulatory element‐binding proteins (SREBP)‐1/2. In HFD‐fed rats, taurine reduced SREBP‐1/2 precursor and mature forms in the livers of HFD‐fed rats. Besides, taurine significantly increased levels of glutathione (GSH), the activity of superoxide dismutase (SOD), and the activity of AMPK and its downstream β‐oxidation genes including peroxisome proliferator‐activated receptor‐α (PPAR‐α) and carnitine palmitoyltransferase (CPT‐1) in the livers of both the control and HFD‐fed rats. In conclusion, taurine protects against HFD‐induced hepatic steatosis stimulating antioxidant levels, and concomitant stimulating hepatic β‐oxidation and suppressing lipid synthesis, mediated by activation of AMPK and suppression of SREBP‐1.     

氢杨梅素改善高脂饮食诱导的肥胖小鼠肝脏脂肪沉积及机制（英文）

有文献报道, SIRT1-AMPK信号通路可能在DHM改善肝脏细胞甘油三酯蓄积、胰岛素抵抗等作用中发挥作用。为此,本课题拟进一步观察DHM对高脂饮食诱导的肥胖小鼠肝脏脂肪沉积的影响,并探讨其可能机制。C57BL/6J小鼠采用普通饲料和高脂饲料喂养,同时分别用或不用低剂量(125 mg/kg)或高剂量(250 mg/kg)的DHM处理16周。实验期间,每两周检测体重一次。16周后,眼眶静脉取血并处死动物,同时取肩胛下、附睾与腹股沟的脂肪并用电子秤进行称重,并记录脂肪重量。全自动生化分析仪检测:血清甘油三酯(triglyceride,TG)、血清总胆固醇(totalcholesterol,TC)、血清高密度脂蛋白(high-densitylipoprotein,HDL)、血清低密度脂蛋白(low-densitylipoprotein,LDL)。取肝脏甲醛固定、HE和油红O染色检测肝脏脂肪沉积情况;比色法检测肝脏MDA和SOD含量; Realtime PCR检测相关指标的基因表达:IL-6、IL-8、TNF-α、乙酰辅酶A羧化酶(acetyl-Co A carboxylase, ACC)、固...     

二氢杨梅素经激活SIRT1-AMPK通路抑制高脂饮食诱导的肥胖小鼠肝脏脂质沉积

目的探究二氢杨梅素(dihydromyricetin,DHM)对高脂饮食诱导的肥胖小鼠肝脏脂质蓄积的作用及其机制。方法C57BL/6J小鼠60只,随机分为6组(n=10):①ND组:正常饲料;②ND+L-DHM组:正常饲料+低剂量DHM(125 mg·kg^-1·d^-1);③ND+H-DHM组:正常饲料+高剂量DHM(250 mg·kg^-1·d^-1);④HFD组:高脂饲料;⑤HFD+L-DHM组:高脂饲料+低剂量DHM;⑥HFD+H-DHM组:高脂饲料+高剂量DHM。记录小鼠体重;16周后,测空腹血脂;计算体脂重量;肝脏HE和油红O染色;荧光定量PCR和Western blot检测肝脏SIRT1、AMPK、ACC、FAS、SREBP-1和PPARα、CPT1的表达。结果与ND组相比,HFD组小鼠体重、体脂、血清TG、TC、HDL水平明显增加;肝脏内脂肪蓄积增加,肝脏SREBP-1c、FAS、ACC1表达增加,而PPARα、CPT1、SIRT1和AMPK表达下降。经DHM处理后,HFD小鼠上述指标发生逆转;但ND小鼠上述指标无明显改变。结论DHM可能通过激活SIRT1-AMPK通路抑制脂质合成,促进脂质分解,改善高脂饮食诱导的肥胖小鼠肝脏脂质沉积。     

Similar changes in muscle lipid metabolism are induced by chronic high‐fructose feeding and high‐fat feeding in C57BL/J6 mice

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Alleviative effect of ciliary neurotrophic factor analogue on high fat‐induced hepatic steatosis is partially independent of the central regulation

Ciliary neurotrophic factor (CNTF) analogues were reported to ameliorate fatty liver in db/db or high‐fat diet‐fed mice. It is generally thought that CNTF exerts its actions centrally. The aim of this study was to investigate whether peripheral effects of CNTF analogues are involved in the therapeutic effect on high fat‐induced hepatic steatosis. The rat model of fatty liver was induced by a high‐fat diet (HFD) for 12 weeks. In the next 2 weeks, rats were fed the HFD along with subcutaneous injection of vehicle or mutant recombinant human CNTF (rhmCNTF 0.05‐0.2 mg/kg per day). Steatotic HepG2 cells were induced by 50% fetal bovine serum (FBS) for 48 hours, and then treated with rhmCNTF for 24 hours. The results showed that after rhmCNTF treatment, hepatic triglyceride (TG) accumulation was attenuated both in vivo and in vitro. RhmCNTF increased protein expression of CPT‐1 and PPARα, and decreased SREBP‐1c, FAS and SCD‐1 in steatotic HepG2 cells. But the production of nitric oxide and 8‐isoPGF_2α in steatotic HepG2 cells was not affected by rhmCNTF. These results suggest that rhmCNTF has a peripheral effect that alleviates fat‐induced hepatic steatosis.     

Leaves of Lippia triphylla improve hepatic lipid metabolism via activating AMPK to regulate lipid synthesis and degradation

Diabetes is a chronic disease associated with triglyceride metabolism disorder, being an etiological factor in fatty liver disease, hypertension, and cardiovascular diseases. Diet-based therapy including energy balance and herbal supplements is a suitable approach to ameliorate progression of the disease. Leaves of Lippia triphylla (lemon verbena) from the family Verbenaceae are a foodstuff used as a tea drink or cooking seasoning, with confirmed safety during long-term use. We report herein the regulatory effect of L. triphylla extract (LTE) and its major compound acteoside (ACT) on abnormal liver lipid metabolism. Both LTE and ACT administration significantly decreased serum and hepatic lipid content, increased the phosphorylation level of the energy metabolism moderator adenosine 5′-monophosphate-activated protein kinase (AMPK), and reduced two major markers of lipid synthesis, viz. acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), with an obvious enhancement in ACC phosphorylation. Furthermore, ACT promoted lipolysis and fatty acid oxidation by increasing messenger RNA (mRNA) expression of adipose triglyceride lipase (ATGL) and carnitine palmitoyltransferase (CPT)-1. These results provide scientific evidence for the development of functional foods containing L. triphylla extract and acteoside for treatment of diabetes-associated lipid metabolism disorder.

     

Gly-Ala-Gly-Val-Gly-Tyr, a novel synthetic peptide, improves glucose transport and exerts beneficial lipid metabolic effects in 3T3-L1 adipoctyes

Recently, it has been demonstrated that fibroin and fibroin-derived peptides enhances insulin sensitivity and glucose metabolism in adipocytes. Here, we show that a synthetic hexapeptide Gly-Ala-Gly-Val-Gly-Tyr (GAGVGY) derived from repetitive amino acid sequence of fibroin improves glucose transport and exerts beneficial lipid metabolic effects in 3T3-L1 adipocytes. GAGVGY increases both basal and insulin-stimulated glucose uptake through enhancement of GLUT1 expression and PI 3-K-dependent GLUT4 translocation, respectively. GAGVGY treatment also led to a significant reduction in the expression of lipogenic genes including sterol regulatory element binding protein-1c (SREBP1c), peroxisome proliferator-activated receptor-γ (PPARγ), and fatty acid synthase (FAS) in mature 3T3-L1 adipocytes, which was corroborated with decreased lipid accumulation by GAGVGY treatment. Additionally, in cells undergoing differentiation, mRNA levels of adipogenic genes including PPARγ and CCAAT/enhancer binding protein α (C/EBPα), stearoyl-CoA desaturase 1 (SCD1), and FAS were suppressed by GAGVGY. Furthermore, GAGVGY increased AMP-activated protein kinase (AMPK) phosphorylation and adiponectin secretion in 3T3-L1 adipocytes. The latter effect was supported with evidence showing increased AMPK activation in C2C12 myocytes treated with 3T3-L1-adipocyte-conditioned medium. Together, our data suggest that GAGVGY has multiple beneficial effects on glucose and lipid metabolism, and would control hyperglycemia without the adverse effect of weight gain.     

蛇床子素通过激活过氧化物酶体增殖物激活受体α调节肝细胞内脂肪酸代谢

目的探讨蛇床子素是否通过激活过氧化物酶体增殖物激活受体(PPAR)α调节肝细胞内的脂肪酸代谢。方法 大鼠肝细胞在用蛇床子素12.5～100μmol.L-1作用24 h后,用比色法测定细胞内甘油三酯(TG)和游离脂肪酸(FFA)含量,用逆转录聚合酶链反应法测定PPARαmRNA表达的变化。PPARα抑制剂MK886 1μmo.lL-1预处理肝细胞2 h后,观察蛇床子素100μmo.lL-1作用24 h后对细胞内TG和FFA含量以及PPARα调控的靶基因包括固醇调节元件结合蛋白(SREBP)-1/2、脂肪酸合酶(FAS)、二脂酰甘油酰基转移酶(DGAT)、肉碱软脂酰转移酶(CPT)-1a、脂肪酸转运蛋白(FATP)4和肝脂肪酸结合蛋白(L-FABP)mRNA表达的影响。结果 蛇床子素12.5～100μmol.L-1可明显降低肝细胞内TG和FFA的含量(P<0.01),同时也能明显增加肝细胞内PPARαmRNA的表达(P<0.01)。在用PPARα抑制剂MK886预处理后,蛇床子素降低肝细胞内TG和FFA的作用则明显被减弱(P<0.01),同时抑制SREBP-1/2,FAS和DGAT mRNA表达的作用明显减弱或完全消失(P<0.01),增加CPT-1a,FATP4和L-FABPmRNA表达的作用也明显减弱或完全消失(P<0.01)。结论 蛇床子素通过激活肝细胞中PPARα后可降低细胞中的TG和FFA含量,其机制与激活PPARα后随后抑制SREBP-1/2,FAS和DGAT的基因表达以及增加CPT-1a,FATP4和L-FABP的基因表达有关。     

Changes in hepatic lipogenic and oxidative enzymes and glucose homeostasis induced by an acetyl‐l‐carnitine and nicotinamide treatment in dyslipidaemic insulin‐resistant rats

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小檗碱对脂质代谢相关基因PPARα和CPTIA表达的影响

目的研究小檗碱(Berberine,Ber)对HepG2细胞的PPARα基因及其调控基因CPTⅠA表达的影响。方法以PPARα激动剂非诺贝特作阳性对照药,采用RT-PCR法研究Ber对HepG2细胞PPARα基因及其调节基因CPTⅠAmR-NA表达影响的时—效和量—效关系。结果非诺贝特明显促进CPTⅠAmRNA表达;Ber也呈浓度和时间依赖性促进CPTⅠAmRNA的表达,而对PPARαmRNA表达无影响;PPARα特异拮抗剂MK-886能阻断非诺贝特和Ber上述作用。结论Ber可能通过激动PPARα促进与脂质代谢相关的靶基因CPTⅠAmRNA的表达。     

Subchronic cadmium exposure upregulates the mRNA level of genes associated to hepatic lipid metabolism in adult female CD1 mice

Cadmium (Cd) is a persistent environmental and occupational contaminant that accumulates in humans and shows adverse effects on health. Accumulating evidence reveals that environmental Cd exposure is associated with hepatic lipid accumulation and metabolic alterations in adult male mice. However, whether Cd exposure induces hepatic lipid accumulation and metabolic alterations in female mice remains poorly understood. In the present study, we aimed to investigate the effects of Cd exposure on insulin resistance, hepatic lipid accumulation and associated metabolic pathways. Female CD1 mice were administrated with CdCl₂ (10 and 100 mg l^–1) by drinking water. We found that Cd exposure did not induce obesity, insulin resistance and hepatic lipid accumulation. By contrary, mice in the Cd‐100 mg l^–1 group presented a significant reduction of the glucose area under the curve during the glucose tolerance test. However, there was a significant elevation in the mRNA level of Fasn and Scd‐1, which were critical genes during hepatic fatty acid synthesis. Moreover, hepatic Fabp1 and Fabp4, two genes for hepatic fatty acid uptake were upregulated in Cd‐treated mice. Of interest, Lpl, a key gene for hepatic lipoprotein lysis, was also upregulated in Cd‐treated mice. Collectively, our results suggest that Cd exposure upregulated mRNA level of genes related to hepatic lipid metabolism although there was no insulin resistance and hepatic lipid accumulation shown in the present study.     

Highly sensitive upregulation of apolipoprotein A-IV by peroxisome proliferator-activated receptor α (PPARα) agonist in human hepatoma cells

Peroxisome proliferator-activated receptor α (PPARα) is a key regulator in hepatic lipid metabolism and a potential therapeutic target for dyslipidemia. However, in humans hepatic PPARα-regulated genes remain unclear. To investigate the effect of PPARα agonism on mRNA expressions of lipid metabolism-related genes in human livers, a potent PPARα agonist, KRP-101 (KRP), was used to treat the human hepatoma cell line, HepaRG cells. KRP did not affect AOX or L-PBE, which are involved in peroxisomal β-oxidation. KRP increased L-FABP, CPT1A, VLCAD, and PDK4, which are involved in lipid transport or oxidation. However, the EC₅₀ values (114–2500 nM) were >10-fold weaker than the EC₅₀ value (10.9 nM) for human PPARα in a transactivation assay. To search for more sensitive genes, we determined the mRNA levels of apolipoproteins, apoA-I, apoA-II, apoA-IV, apoA-V, and apoC-III. KRP had no or little effect on apoA-I, apoC-III, and apoA-II. Interestingly, KRP increased apoA-IV (EC₅₀, 0.99 nM) and apoA-V (EC₅₀, 0.29 nM) with high sensitivity. We identified apoA-IV as a PPARα-upregulated gene in a study using PPARα siRNA. Moreover, when administered orally to dogs, KRP decreased the serum triglyceride level and increased the serum apoA-IV level in a dose-dependent manner. These findings suggest that apoA-IV, newly identified as a highly sensitive PPARα-regulated gene in human livers, may be one of the mechanisms underlying PPARα agonist-induced triglyceride decrease and HDL elevation.     

Eicosapentaenoic acid improves hepatic steatosis independent of PPARα activation through inhibition of SREBP-1 maturation in mice

Eicosapentaenoic acid (EPA) in fish oil is known to improve hepatic steatosis. However, it remains unclear whether such action of EPA is actually caused by peroxisome proliferator-activated receptor α (PPARα) activation. To explore the contribution of PPARα to the effects of EPA itself, male wild-type and Ppara-null mice were fed a saturated fat diet for 16 weeks, and highly (>98%)-purified EPA was administered in the last 12 weeks. Furthermore, the changes caused by EPA treatment were compared to those elicited by fenofibrate (FF), a typical PPARα activator. A saturated fat diet caused macrovesicular steatosis in both genotypes. However, EPA ameliorated steatosis only in wild-type mice without PPARα activation, which was evidently different from numerous previous observations. Instead, EPA inhibited maturation of sterol-responsive element-binding protein (SREBP)-1 in the presence of PPARα through down-regulation of SREBP cleavage-activating protein and site-1 protease. Additionally, EPA suppressed fatty acid uptake and promoted hydrolysis of intrahepatic triglycerides in a PPARα-independent manner. These effects were distinct from those of fenofibrate. Although fenofibrate induced NAPDH oxidase and acyl-coenzyme A oxidase and significantly increased hepatic lipid peroxides, EPA caused PPARα-dependent induction of superoxide dismutases, probably contributing to a decrease in the lipid peroxides. These results firstly demonstrate detailed mechanisms of steatosis-ameliorating effects of EPA without PPARα activation and ensuing augmentation of hepatic oxidative stress.     

Effect of oxymatrine on lipid metabolism regulated genes in liver of fat-induced insulin resistance in ApoE-/-mice北大核心CSCD

Aim To investigate the effect of oxymatrine on lipid metabolism regulated genes in liver in fat-induced insulin resistance in ApoE-/- mice. Methods Seventeen C57BL/6J male mice were selected in normal control group. Sixty-eight ApoE-/- mice with high fat diet for 16 weeks, were randomly divided into model group, oxymatrine low, middle and high dose groups. Then they were gavaged for 8 weeks. Body weight and general biochemical indicators were determined in mice. The mRNA and protein expression levels of LPL, FAT/CD36, CPT1, UCP2, SREBP-1 c, FAS and ACC were examined by real-time PCR and Western blot in the liver. Results Compared with model group, oxymatrine reduced body weight (BW) , fasting blood glucose (FBG), cholesterol (TC) , triglyceride (TG) , free fatty acids (FFA), fasting plasma insulin (FINS) and insulin resistance index(HOMA-IR) (P < 0. 05) , while improved glucose infusion rate (GIR) . Oxymatrine down-regulated the mRNA and protein expression of LPL, FAT/CD36, UCP2, SREBP-1c, FAS and ACC(P <0. 05) ,and up-regulated the mRNA and protein expression of CPT1 in varying degrees (P < 0. 05). Conclusion Oxymatrine can regulate the expression of lipid metabolism regulated genes in liver and improve insulin resistance in ApoE-/- mice induced by high fat diet.