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Insulin and glucocorticoids differentially regulate leptin transcription and secretion in brown adipocytes

MARION BUYSE^*, SAY VIENGCHAREUN, ANDRÉ BADO^* and MARC LOMBÈS¹

^* INSERM U 410 and
INSERM U 478, Institut Fédératif de Recherche ‘Cellules épithéliales’ IFR2, Faculté de Médecine Xavier Bichat, Paris cedex 18, France

¹Correspondence: INSERM U 478, Institut Fédératif de Recherche ‘Cellules épithéliales’ IFR2, Faculté de Médecine Xavier Bichat, 16, rue Henri Huchard 75870, Paris cedex 18, France. E-mail: mlombes{at}bichat.inserm.fr

Leptin, the ob gene product, is produced by adipose tissue and is submitted to a complex hormonal and metabolic regulation. Leptin plays a critical role in the balance of body weight. Here we report on secretion and hormonal regulation of leptin by brown adipocytes. Using the recently established T37i cell line, we show that leptin expression and secretion occurred as a function of cell differentiation. In differentiated T37i cells, insulin induced leptin release (0.25 ng/10⁶ cells/h) in a concentration-dependent manner (EC₅₀=0.1 nM), and this was totally suppressed by ß₃-adrenergic ligand, thiazolidinedione, cycloheximide, or actinomycin D. Insulin induced a strong, rapid (within 2 h) but transient fivefold increase in leptin mRNA levels. This transcriptional control of ob gene expression by insulin involved both phosphatidylinositol 3-kinase- and MAP kinase-dependent pathways. Glucocorticoids inhibited both insulin-stimulated leptin secretion and ob gene expression without affecting leptin mRNA stability (t_1/2=3h05). Altogether, our results demonstrate that brown adipocytes express and secrete leptin, whose hormonal regulation clearly differs from that described in white adipose tissue. These findings point to tissue-specific molecular mechanisms and suggest that leptin might exert direct effects on energy homeostasis through an autocrine mechanism.—Buyse, M., Viengchareun, S., Bado, A., Lombès, M. Insulin and glucocorticoids differentially regulate leptin transcription and secretion in brown adipocytes.

Key Words: cell line • uncoupling protein • ob gene • signaling pathway • obesity

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