Insulin resistance in insulin-resistant and diabetic hamsters (Mesocricetus auratus) is associated with abnormal hepatic expression of genes involved in lipid and glucose metabolism.

Fat-induced hepatic insulin resistance (FIHIR) in obesity induced by high-fat diet leads to ectopic lipid accumulation and may contribute to the pathogenesis of type 2 diabetes. We examined the alterations in hepatic gene expression involved in FIHIR by using obese insulin-resistant and diabetic hamsters that received high-fat diet with or without low-dose streptozotocin. Microarray analysis and confirmatory real-time RT-PCR indicated that increased mRNA levels of sterol regulatory element-binding proteins (SREBPs) and decreased mRNA levels of liver X receptor (LXR alpha) and peroxisome-proliferator-activated receptor (PPAR alpha) occurred in FIHIR in insulin-resistant and diabetic hamsters. Expression levels of hepatic LXR alpha, SREBPs, and PPAR alpha differed significantly between insulin-resistant and diabetic hamsters. Expression of LXR alpha, SREBPs, and PPAR alpha all change in FIHIR associated with hepatic lipid accumulation in insulin-resistant and diabetic hamsters in which disease is induced by high-fat diet and streptozotocin injection.