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 pr ocess to provide fuel to other organs and to deliver substrates to liver fo r gluconeogenesis (glycerol) and lipoprotein synthesis (free fatty acids). The release of glycerol and free fatty acids is intensively regulated by ho rmones and agents. In man, the major hormones are insulin (inhibition of li polysis) and catecholamines (stimulation of lipolysis). Physiological facto rs such as dieting, physical exercise and ageing also regulate lipolysis Th e lipolytic process is modified in pathological conditions, e.g. obesity (b oth upper and lower obesity), diabetes (non- and insulin-dependent diabetes mellitus), and dyslipidaemia (in particular, familial combined hyperlipida emia). The regulation of lipolysis is complex because of the heterogeneity of fat depots (visceral versus subcutaneous), which may contribute to the w ell-known gender differences in ac cumulation of fat. Sin ce visceral fat d epot is directly drained into the liver and has a high turnover of visceral triglycerides, "portal" free fatty acids seem to he an important pathophys iological factor in common complications of obesity (in particular, metabol ic syndrome). New advances in genetic studies indicate that polymorphisms i n several genes encoding for proteins that regulate the lipolysis process a re important for the development of obesity and its complications.