[Metabolic and trophic role of catecholamines in the development of white adipose tissue]

The fat cell is of key significance to the physiologist investigating the mechanisms controlling lipid storage, mobilization and utilization as well as other functions of the adipose tissue. Insulin and catecholamines are the major hormonal regulators of lipolysis. Four adrenoceptor subtypes are involved in the adrenergic regulation of fat cell lipolysis. The control of adenylyl cyclase activity involves stimulatory beta 1-, beta 2- and beta 3-adrenergic receptors and inhibitory alpha 2-adrenergic receptors. Their control of lipolysis is subjected to variations according to the anatomical localization of adipose tissue deposits. In humans, lipolysis differs in visceral and subcutaneous deposits. Changes in beta- and alpha 2-adrenoceptor ratios and function have been proposed to explain the lipolytic disturbances. Human and rodent white adipocytes differ dramatically with respect to the balance between alpha 2 and b-adrenergic receptors. Human adipocytes express mainly alpha 2 and few b3-adrenergic receptors while the reverse is true for rodent adipocytes. Preadipocyte alpha 2-adrenergic receptor stimulation initiates proliferation mediated by MAPkinase activation and cytoskeleton re-arrangements. We have generated transgenic mice on a b3-adrenergic receptor gene knock-out background which express human alpha 2-adrenergic receptors selectively in white and brown fat cells by using an adipocyte-specific promoter. No phenotype was noticed in the mice fed with a standard diet, by contrast a large increase in body weight was observed when the animals are fed with a high fat diet. The weight gain concerns fat deposits and is mainly characterized by a large increase in fat cell number. This phenotype is due to an interaction between two genes and the diet since the unique combination of a high fat diet, absence of b3-adrenergic receptors and presence of alpha 2-adrenergic receptors promotes hyperplastic development of fat deposits and increased weight gain.