Regulation of lipolysis in humans. Pathophysiological modulation in obesity, diabetes, and hyperlipidaemia

Adipose tissue is considered as the body's largest storage organ for energy in the form of triglycerides, which are mobilised through the lipolysis process to provide fuel to other organs and to deliver substrates to liver for gluconeogenesis (glycerol) and lipoprotein synthesis (free fatty acids). The release of glycerol and free fatty acids is intensively regulated by hormones and agents. In man, the major hormones are insulin (inhibition of lipolysis) and catecholamines (stimulation of lipolysis). Physiological factors such as dieting, physical exercise and ageing also regulate lipolysis. The lipolytic process is modified in pathological conditions, e.g. obesity (both upper and lower obesity), diabetes (non- and insulin-dependent diabetes mellitus), and dyslipidaemia (in particular, familial combined hyperlipidaemia). The regulation of lipolysis is complex because of the heterogeneity of fat depots (visceral versus subcutaneous), which may contribute to the well-known gender differences in accumulation of fat. Since visceral fat depot is directly drained into the liver and has a high turnover of visceral triglycerides, "portal" free fatty acids seem to be an important pathophysiological factor in common complications of obesity (in particular, metabolic syndrome). New advances in genetic studies indicate that polymorphisms in several genes encoding for proteins that regulate the lipolysis process are important for the development of obesity and its complications.