ABSTRACT
Objective To study the influences of fenofibrate on oxidative stress and endoplasmic reticulum stress in livers of hyperlipidemic rats. Methods Male SD rats were fed with high-fat diet for 12 weeks to induce a model of hyperlipidemia, then divided into control group, high-fat diet group with another four-week high-fat diet and fenofibrate group, in which rats were treated with fenofibrate [100 mg / (kg·d)] for 4 weeks. Then improvement of insulin resistance was detected in rats with GTT and ITT experiment. The serum levels of glucose (GLU), fasting insulin (FINS),triglyceride (TG) and total cholesterol (TC) were detected. The pathological changes of livers were detected with Oil Red O staining. The oxidative stress indices such as T-SOD, Mn-SOD, GSH and T-AOC were detected with liver homogenate. The expression of GRP78 was detected with real-time quantification RT-PCR and Western blot analysis respectively. Results Compared with rats with high-fat-diet, rats after fenofibrate treatment showed obviously improved insulin resistance, lower serum level of TG, TC and FINS (P 0.05). The expression of GRP78 at mRNA and protein levels were increased significantly after fenofibrate treatment (P < 0.05). Conclusions Fenofibrate has significant effects on improving insulin resistance and lipid regulation, which might be related to decreased oxidative stress and subsequent endoplasmic reticulum stress.
ABSTRACT
Objective To study whether the protective effects of fenofibrate on insulin resistance in mice of nonal-coholic fatty liver disease(NAFLD) are related to endoplasmic reticulum stress (ERS). Methods Male C57BL/6 mice were fed with high-calorie and high-cholesterol diet ( HCD) to induce a model of NAFLD, then one of those two groups from HCD was treated with fenofibrate 40 mg/( kg · d ) for 2 weeks ( HCF ) . Glucose tolerance test (GTT) and insulin tolerance test (ITT) were used to analyze the improvement on insulin resistance. The serum levels of triglyceride ( TG) , total cholesterol ( TC) , high density lipoprotein-cholesterol ( HDL-C) , low density lip-oprotein-cholesterol ( LDL-C) , alanine aminotransferase ( ALT) and aspartic transaminase ( AST) were detected. The pathological changes of livers were detected with HE and Oil Red O staining, the mRNA and protein expression of peroxisome proliferator-activated receptorα( PPARα) , glucose regulated protein 78 ( GRP78 ) and transcription factors GADD153 ( CHOP) were detected with real-time quantification PCR and Western blot analysis respectively. Results Compared with the SCD mice, the HCD mice showed significant insulin resistance, higher serum levels of TG, TC and LDL-C (P<0. 01, P<0. 05), lower serum level of HDL-C (P<0. 01), micro-and macrovesicular steatosis, ballooned hepatocytes and infiltration of inflammatory cells were observed in the liver, the expressions of PPARα and GRP78 at mRNA and protein levels were decreased (P<0. 05), however, the expressions of CHOP at mRNA and protein levels were increased ( P<0 . 05 ) . Fenofibrate intervention significantly improved insulin resist-ance and decreased the serum level of TG ( P<0. 05 ) . Fenofibrate also alleviated hepatic steatosis and inflammato-ry infiltration, and increased the mRNA and protein expressions of PPARα and GRP78, decreased the mRNA and protein expression of CHOP ( P<0 . 05 ) . Conclusion Fenofibrate significantly improves insulin resistance and de-creases the serum level of TG in NAFLD mice, which may be related to activating PPARα and relieving ERS.