Development and characterization of a novel animal model of diet-induced insulin resistant diabetes and metabolic dyslipidemia: Mechanistic interactions between dietary fructose, fat and cholesterol, and the possible role of liver X receptor in the induction of metabolic syndrome.

摘要

The underlying mechanisms of the metabolic syndrome are poorly understood. To further explore these mechanisms, a diet-induced hamster model was studied using the FFC diet (40% fructose, 30% fat, 0.25% cholesterol) over a period of 2 to 20 weeks. Results indicated evidence of hepatic steatosis, elevations in plasma triglyceride (TG), cholesterol, very low density lipoprotein (VLDL)-TG, and increased levels of apolipoprotein B-100 (apoB). Metabolic studies showed alterations in both newly synthesized lipids and lipoprotein metabolism. Hepatic gene expression showed elevations of lipogenic enzymes, and evidence of hepatic insulin resistance.; The nuclear receptor LXR is known to be involved in the regulation of signaling and lipid pathways found to be altered in the FFC diet study; a second study was performed to examine LXRalpha-induced changes using the specific LXR agonist, TO901317. LXR activation was found to stimulate lipogenesis, increase newly synthesized apoB-containing lipoprotein particles, and cause a dysregulation of insulin signaling.