Adiponectin gene expression is inhibited by β‐adrenergic stimulation via protein kinase A in 3T3‐L1 adipocytes

FEBS Letters

Fasshauer, Mathias²  Eszlinger, Markus²  Neumann, Susanne²  Paschke, Ralf²  Klein, Johannes¹ 

[1] Medical University of Lübeck, Department of Internal Medicine I, 23538 Lubeck, Germany;University of Leipzig, Department of Internal Medicine III, Ph.-Rosenthal-Str. 27, 04103 Leipzig, Germany

关键词: Adiponectin;    β-Adrenergic receptor;    Insulin resistance;    Obesity;    3T3-L1 adipocyte;    DMEM;    Dulbecco's modified Eagle's medium;    FFA;    free fatty acids;    GS-protein;    stimulatory guanine nucleotide-binding protein;    PKA;    protein kinase A;    RT-PCR;    reverse transcription-polymerase chain reaction;   

DOI  :  10.1016/S0014-5793(01)02960-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Recently, it has been shown that the fat-derived factor adiponectin is downregulated in insulin resistance and obesity and that replenishment of this adipocytokine reverses insulin resistance in mice. Growing evidence, on the other hand, suggests that raised levels of catecholamines due to increased activity of the sympathetic nervous system are an integral part in the development of insulin resistance. To clarify whether catecholamines might exert their insulin resistance-inducing effects at least partly via downregulation of adiponectin gene expression, 3T3-L1 adipocytes were treated with isoproterenol, and adiponectin mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction. In fact, isoproterenol treatment reduced the level of adiponectin mRNA by about 75% in a dose-dependent fashion with significant inhibition detectable at concentrations as low as 10 nM isoproterenol. Furthermore, the inhibitory effect of isoproterenol was almost completely reversed by pretreatment of 3T3-L1 cells with the β-adrenergic antagonist propranolol and the protein kinase A (PKA) inhibitor H-89. Moreover, the effects of isoproterenol could be mimicked by stimulation of stimulatory guanine nucleotide-binding (G_S)-proteins with cholera toxin and adenylyl cyclase with forskolin. Thus, our results suggest that adiponectin gene expression is severely suppressed by β-adrenergic agents via activation of a G_S-protein–PKA-dependent pathway. The data support a possible role of adiponectin in catecholamine-induced insulin resistance.

【 授权许可】

Unknown