Signalling mechanisms regulating lipolysis

Adipose tissue plays an important role providing energy to other tissues and functioning as an energy reserve organ. The energy supply is produced by triglycerides stored in a large vacuole representing approximately 95% of adipocyte volume. In the fasting period, triglyceride hydrolysis produces glycerol and free fatty acids which are important oxidative fuels for other tissues such as liver, skeletal muscle, kidney and myocardium. Hormone-sensitive lipase (HSL) is the enzyme that hydrolyzes intracellular triacylglycerol and diacylglycerol, and is one of the key molecules controlling lipolysis. Hormones and physiological factors such as dieting, physical exercise and ageing regulate intensively the release of glycerol and free fatty acids from adipocytes. One of the best known mechanisms that activate lipolysis in the adipocyte is the cAMP dependent pathway. cAMP production is modulated by hormone receptors coupled to Gs/Gi family of GTP binding proteins, such as -adrenergic receptors, whereas cAMP degradation is controlled by modulation of phosphodiesterase activity, increased by insulin receptor signalling. cAMP activates PKA which activates HSL by promoting its phosphorylation. Hormonal control of lipolysis can also be achieved by receptors coupled G proteins of the Gq family, through molecular mechanisms that involve PKC and MAPK, which are currently under investigation. cGMP and PKG have also been found to activate lipolysis in adipocytes. In this review we have compiled data from literature reporting both the classical and the alternative mechanisms of lipolysis. (c) 2005 Elsevier Inc. All rights reserved.