Chapter 6 - Hormonal control of lipid degradation

Abstract

Publisher Summary This chapter focuses on the hormonal control mechanisms of lipid degradation. To a large extent this control is accomplished through regulation of the degradation of stored adipocyte lipids to free fatty acids (FFA) and glycerol, in the process of adipose tissue lipolysis. The rate of this process directly reflects the activity of the rate-limiting enzyme—the hormone-sensitive lipase (HSL). The hydrolysis of the monoacylglycerols produced is mainly catalyzed by a separate, specific monoacylglycerol lipase. The reversible cyclic AMP-mediated phosphorylation of HSL in adipose tissue is indeed the only major important mechanism for the short-term hormonal control of the lipolysis of stored lipids. The net dephosphorylation of HSL causes insulin's anti-lipolytic effect. The fast-acting lipolytic hormones and insulin affect the activity of HSL by controlling the phosphorylation of a single serine residue, the phosphorylation state of which is regulated by cyclic AMP-dependent protein kinase (PK) and protein phosphatase types 1, 2A, and 2C. Cyclic AMP-independent PKs phosphorylates the enzyme on one additional site, but this phosphorylation does not appear to affect the activity of the enzyme directly, which is known as silent phosphorylation. The mechanisms by which insulin exerts its effect on HSL are the isolated fat cell system, in combination with the techniques developed for following the phosphorylation state and activity of HSL.