What is the mechanism underlying the turnover of β-adrenergic receptor on hypertrophied primary adipocytes?

本研究旨在探讨β_2-肾上腺素能受体（β_2-AR）的转运对肥胖哺乳动物高脂饮食诱导的肥厚脂肪细胞（HA）脂肪分解的调节作用。实验动物（C57BL/6J小鼠）随机分为正常饮食组和高脂饮食组，从附睾脂肪组织中分离脂肪细胞。低浓度（10 nM）异丙肾上腺素（ISO）刺激的脂解在HA细胞中显著高于非肥厚对照（NHC）细胞。与NHC相比，高浓度（1 μM） ISO对HA的脂解作用明显减弱。在此条件下，在膜组分中，与NHC相比，HA中β_2-AR水平显著降低，同时β_2-AR/ β_2-AR复合物水平升高，它们是激动剂诱导的β_2-AR从质膜转运到细胞质溶胶的促进剂。这些结果表明，高浓度ISO下的β_2-AR内化与HA中脂溶反应水平降低有关，这一现象是肥胖哺乳动物体内脂肪代谢水平降低的机制之一。

The purpose of the current study is to investigate the trafficking of β_2-adrenergic receptor (β_2-AR) can regulate the lipolysis in high fat diet-induced hypertrophied adipocytes (HA) that are observed in obese mammals. The animals (C57BL/6J mice) were randomly divided into two groups : a normal diet intake and high fat diet intake, and adipocytes were isolated from epididymal adipose tissue. Low concentration (10 nM) of Isoproterenol (ISO)-stimulated lipolysis was significantly elevated in HA than that in non hypertrophied control (NHC) cells. In contrast, lipolysis in HA was significantly attenuated in high concentration (1 μM) of ISO compared with NHC. Under this condition, in membrane fraction, the levels of β_2-AR was significantly reduced in HA compared with NHC, accompanied by increased levels of β-arrestin-2 and β_2-AR/β-arrestin-2 complex, which are accelerator of agonist-induced trafficking of the β_2-AR from plasma membrane to cytosol. These results suggest that trafficking i.e., internalization of β_2-AR, with high concentration of ISO would be associated with reduced levels of lipolytic response in HA, and that this phenomenon is one of the mechanism underlying lower levels of fatmetabolism in obese mammals in vivo.