[The mechanism of and relationship between lipid metabolism genes expression and insulin resistance in high fat-fed mice].

OBJECTIVE: To observe the relationship between changes of genes expression related to lipid metabolism and insulin resistance induced by high fat diet in SD rats.

METHODS: Normal 8-week old male SD rats were randomly divided into 3 groups. They were fed with normal chow (NC, n = 10), high fat diet (HF, n = 10) and high fat diet supplemented with pioglitazone 15 mg x kg(-1) x d(-1) (HP, n = 12). The TG content of liver and skeletal muscle of the rats was measured. Glucose infusion rate (GIR) was used to evaluate the insulin sensitivity by using euglycemic-hyperinsulinemic clamp method. Genes expression was investigated using real-time PCR method.

RESULTS: After high fat feeding for 20 weeks, the serum TG, the content of TG in the liver and skeletal muscle of the rats in the HF group increased 0.45, 2.28 and 9.31 fold respectively as compared with those in the NC group. The change of TG content in the liver and skeletal muscle was associated with the reduction of GIR [(6.16 +/- 0.75) mg x kg(-1) x min(-1) vs (15.82 +/- 2.10) mg x kg(-1).min(-1) (P < 0.01)]. As compared with the NC group, the expression of hormone-sensitive lipase (HSL) and fatty-acid synthase (FAS) gene in the HF group was enhanced by 28.2% and 21.3%, respectively (P < 0.05). In addition, the expression of acetyl-CoA carboxylase1 (ACC1) mRNA in the liver increased 48.3% (P < 0.05), increased 101.1% (P < 0.01) and carnitine palmitoyltransferase 1 (CPT-1) decreased 71.0% (P < 0.01) in the skeletal muscle in the rats of HF group. As compared with those in the HF group, GIR increased 1.54 fold in the HP group and on the contrary, serum TG, liver TG and muscle TG decreased about 66%, 64.5% and 59.6% respectively in the HP group (P < 0.05). Accordingly, the expression of FAS and HSL in the adipose tissue and the expression of ACC1 in the liver were reduced (P < 0.05) and the expression of CPT-1 was enhanced and ACC2 was reduced in the muscle (P < 0.01) in the HP group.

CONCLUSIONS: The changing expression of genes related to lipid metabolism may play a role in the accumulation of lipids in non-adipose tissue and the induction of insulin resistance in rats fed with high fat diet.