OBJECTIVETo study the relationship between hepatic insulin resistance induced by high fat diet and the expression of genes involving hepatic glucose output.

METHODSNormal 8-week-old male SD rats were randomly divided into two groups, i.e, normal chow group (NC, n = 10) and high fat diet group (HF, n = 10). They were fed for 28 weeks. Body weight and fasting blood glucose (FBG) were measured. At the end of the experiment, the rats were sacrificed and their fasting insulin (INS) and triglycerides (TG) were measured. Hepatic insulin sensitivity was measured by tissue uptake of 3H-2-deoxyglucose and the content of hepatic glycogen was measured using the anthrone method. Gene expression was investigated by using the semi-quantitative RT-PCR method.

RESULTSAs compared with NC group, CF group rats developed visceral obesity which was accompanied by higher plasma TG. FBG in CF group increased starting from the 18th week (NC 4.77+/-63 mmol/L vs HF 5.45+/-87 mmol/L, P < 0.05). The rate of uptake of 3H-2-deoxyglucose in livers decreased by 51% in the HF group. The content of hepatic glycogen increased by 92.4% (P < 0.01). The level of phosphoenolpyruvate carboxykinase (PEPCK) and PGC-1a mRNA increased by 41.5% and 30.8%, respectively (P < 0.05).

CONCLUSIONA high fat diet induced expressions of PGC-1a and PEPCK. It suggests that gluconeogenesis may play a role in the increase of hepatic glucose output and FBG.