The role of mTOR in lipid homeostasis and diabetes progression.

Abstract

Metabolic diseases, such as type 2 diabetes, cardiac dysfunction, hypertension, and hepatic steatosis, share one critical causative factor: abnormal lipid partitioning, that redistribution of triglycerides from adipocytes to nonadipose peripheral tissues. Lipid overload of these tissues causes a number of pathological effects collectively known as lipotoxicity. If we find the way to correct lipid partitioning, we will restrain metabolic diseases, improve life quality and life expectancy and radically reduce healthcare costs. Lipid partitioning in the body is maintained by tightly regulated and balanced rates of de novo lipogenesis, lipolysis, adipogenesis, and mitochondrial oxidation primarily in fat and liver. Recent studies highlighted in this review have established mTOR as a central regulator of lipid storage and metabolism. Increased activity of mTOR in obesity may compensate for the negative consequences of overnutrition, whereas dysregulation of mTOR may lead to abnormal lipid partitioning and metabolic disease.