Atherogenic lipid metabolism in obesity

Abstract

Atherogenic dyslipidemia, characterized by increased triglyceride-rich lipoproteins (TRLs), increased small dense low density lipoprotein (LDL), and low levels of high density lipoprotein (HDL), is common in obesity. This constellation is often accompanied by insulin resistance and associated with substantially increased risk for cardiovascular disease in these individuals. This chapter details the known molecular mechanisms of adipose tissue and hepatic function, as it pertains to apoB-containing lipoprotein assembly and metabolism, both in the healthy as well as in the obese, insulin resistant state. The mechanisms connecting obesity, insulin resistance, and dyslipidemia are incompletely understood, but are thought to be driven by (a) increased flux of free fatty acids (FFAs) from adipose tissue to liver driving hepatic overproduction of very low density lipoprotein (VLDL), (b) impaired catabolism of atherogenic lipoprotein remnants, and (c) hypercatabolism of HDL. The pathophysiology of each of these, and the implications for cardiovascular disease risk and therapeutics are discussed. The present paradigm is likely oversimplified, and a more thorough understanding of the physiological and molecular mechanisms is critical for improving our approach to managing the influence of obesity on lipoprotein metabolism, and to the development of appropriate therapeutic approaches. © 2011 Springer Science+Business Media, LLC.