Metabolic effects of dietary cholesterol in an animal model of insulin resistance and hepatic steatosis.

Although the atherogenic role of dietary cholesterol has been well established, its diabetogenic potential and associated metabolic disturbances have not been reported. Diet-induced hamster models of insulin resistance and dyslipidemia were employed to determine lipogenic and diabetogenic effects of dietary cholesterol. Metabolic studies were conducted in hamsters fed diets rich in fructose (40%), fat (30%), and cholesterol (0.

LXRalpha activation perturbs hepatic insulin signaling and stimulates production of apolipoprotein B-containing lipoproteins.

Liver X receptor-alpha (LXRalpha) is considered a master regulator of hepatic lipid metabolism; however, little is known about the link between LXR activation, hepatic insulin signaling, and very low-density lipoprotein (VLDL)-apolipoprotein B (apoB) assembly and secretion. Here, we examined the effect of LXRalpha activation on hepatic insulin signaling and apoB-lipoprotein production. In vivo activation of LXRalpha for 7 days using a synthetic LXR agonist, TO901317, in hamsters led to increased plasma triglyceride (TG; 3.

Lipid and lipoprotein dysregulation in insulin resistant states.

Insulin resistant states are commonly associated with an atherogenic dyslipidemia that contributes to significantly higher risk of atherosclerosis and cardiovascular disease. Indeed, disorders of carbohydrate and lipid metabolism co-exist in the majority of subjects with the "metabolic syndrome" and form the basis for the definition and diagnosis of this complex syndrome. The most fundamental defect in these patients is resistance to cellular actions of insulin, particularly resistance to insulin-stimulated glucose uptake.

Fructose, insulin resistance, and metabolic dyslipidemia.

Obesity and type 2 diabetes are occurring at epidemic rates in the United States and many parts of the world. The "obesity epidemic" appears to have emerged largely from changes in our diet and reduced physical activity. An important but not well-appreciated dietary change has been the substantial increase in the amount of dietary fructose consumption from high intake of sucrose and high fructose corn syrup, a common sweetener used in the food industry.