Abstract

The sympathetic nervous system controls lipolysis in fat by activation of four adrenergic receptors: β1, β2, β3, and α2. During pregnancy, maternal metabolism presents anabolic and catabolic phases, characterized by modifications of fat responsiveness to catecholamines. The contributions of the four adrenergic receptors to adipocyte responsiveness during pregnancy have never been studied. Our aim was to evaluate the influence of pregnancy on adrenergic receptor-mediated lipolysis in rabbit white adipocytes. Functional studies were performed using subtype-selective and non-selective adrenergic receptor agonists. Overall adrenergic responsiveness was measured with the physiological agonist epinephrine. Non-adrenergic agents were used to evaluate different steps of the lipolytic cascade. The α2- and β1/β2-adrenergic receptor numbers were determined with selective radioligands. Non-adrenergic agents revealed that pregnancy induced an intracytoplasmic modification of the lipolytic cascade in inguinal but not in retroperitoneal adipocytes. Pregnancy induced an increase in β1- and specially β3-mediated lipolysis. The amounts of adipocyte β1/β2- and α2-adrenergic receptors were increased in pregnant rabbits. Epinephrine effects revealed an increased contribution of α2-adrenergic receptor-mediated antilipolysis in adipocytes from pregnant rabbits. These results indicate that pregnancy regulates adipocyte responsiveness to catecholamines mainly via the α2- and β3-adrenergic pathways. Pregnancy induces an intracytoplasmic modification of the lipolytic cascade, probably via hormone-sensitive lipase, with differences according to fat location.—Bousquet-Mélou, A., C. Muñoz, J. Galitzky, M. Berlan, and M. Lafontan. Pregnancy modifies the α2-β-adrenergic receptor functional balance in rabbit fat cells. J. Lipid Res. 1999. 40: 267–274.

Highlights

  • The sympathetic nervous system controls lipolysis in fat by activation of four adrenergic receptors: ␤1, ␤2, ␤3, and ␣2

  • Lipolytic responses initiated by non-adrenergic agents In order to evaluate the different steps of the lipolytic pathway, lipolysis induced by dibutyryl cAMP, an analogue of cAMP that directly activates the cAMP-dependent protein kinase, and forskolin, which is a direct activator of the catalytic subunit of adenylyl cyclase, were measured

  • Spontaneous and activated lipolysis were significantly enhanced in pregnant rabbits compared to virgins

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Summary

Introduction

The sympathetic nervous system controls lipolysis in fat by activation of four adrenergic receptors: ␤1, ␤2, ␤3, and ␣2. Epinephrine effects revealed an increased contribution of ␣2-adrenergic receptor-mediated antilipolysis in adipocytes from pregnant rabbits These results indicate that pregnancy regulates adipocyte responsiveness to catecholamines mainly via the ␣2- and ␤3-adrenergic pathways. Pregnancy is a physiological state characterized by modifications in maternal adiposity, leading to an increase in adipose tissue mass during the earlier phase and followed by a decrease of fat mass during the late phase These two metabolic phases are associated with adaptations of fat cell functions, resulting respectively in a predominance of lipogenic and lipolytic functions [17]. Fat cell responsiveness to catecholamines results from the balance between ␤- and ␣2-

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