Study on relationship between fat-rich diet-induced nonalcoholic fatty liver disease and endoplasmic reticulum stress in rats / 中华消化杂志

ABSTRACT

Objective To establish the nonalcoholic fatty liver disease(NAFLD) model in SD rats and to investigate if endoplasmic reticulum stress(ERS) plays a role in the pathogenesis of NAFLD. Methods A total of 36 male SD rats were randomly divided into 4 groups normal control group 1(N1,n=8), normal control group 2 (N2,n=8), model group 1(M1,n=10) and model group 2(M2,n=10). The two control groups were fed with normal diets, whereas the two model groups were provided diets enriched in fat (10% lard oil and 2% cholesterol). The rats in N1 and M1 groups were sacrificed at the 12th week, and those in N2 and M2 groups were sacrificed at the 20th week. The serum alanine aminotransferase (ALT), aspartate aminotransferase(AST), alkaline phosphatase (ALP), total protein (TP), triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) were measured. The steatosis, immflamation and fibrosis of the liver were observed with HE and Masson staining. The expressions of GRP78, CHOP and procaspase-12 mRNA were tested using real-time PCR and the activation of procaspase-12 protein was detected by Western blot. Results At the 12th week, the liver index and the serum levels of ALT, AST,ALP,TP,TC,LDL in M1 group were significantly higher than those in N1 group (P<0.01), but HDL level was significantly lower in M1 group than that in N1 group (P<0.01). At the 20th week, the concentrations of TC and LDL in M2 group were significantly increased in comparison with N2 group. The histochemical study revealed that the hepatic steatosis and inflammation in M1 and M2 groups were more serious than those in N1 and N2 goups(P<0.01). The slight fibrosis was seen in M2 group. At the 12th and 20th weeks, the expressions of GRP78,CHOP and procaspase-12 mRNA and protein in M1 and M2 groups did not differ in N1 and N2 groups. Conclusions The fat-rich diet might successfully induce NAFLD in rats and there is no ERS observed in the study, which suggests that ERS may not be involved in the pathogenesis of NAFLD.