脂肪细胞中粘附 G 蛋白偶联受体的库及其功能相关性。
The repertoire of Adhesion G protein-coupled receptors in adipocytes and their functional relevance.
机构信息
Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, Leipzig University, Leipzig, Germany.
Institute for Medical Physics and Biophysics, Medical Faculty, Leipzig University, Leipzig, Germany.
出版信息
Int J Obes (Lond). 2020 Oct;44(10):2124-2136. doi: 10.1038/s41366-020-0570-2. Epub 2020 Mar 19.
BACKGROUND
G protein-coupled receptors (GPCR) are well-characterized regulators of a plethora of physiological functions among them the modulation of adipogenesis and adipocyte function. The class of Adhesion GPCR (aGPCR) and their role in adipose tissue, however, is poorly studied. With respect to the demand for novel targets in obesity treatment, we present a comprehensive study on the expression and function of this enigmatic GPCR class during adipogenesis and in mature adipocytes.
METHODS
The expression of all aGPCR representatives was determined by reanalyzing RNA-Seq data and by performing qPCR in different mouse and human adipose tissues under low- and high-fat conditions. The impact of aGPCR expression on adipocyte differentiation and lipid accumulation was studied by siRNA-mediated knockdown of all expressed members of this receptor class. The biological characteristics and function of mature adipocytes lacking selected aGPCR were analyzed by mass spectrometry and biochemical methods (lipolysis, glucose uptake, adiponectin secretion).
RESULTS
More than ten aGPCR are significantly expressed in visceral and subcutaneous adipose tissues and several aGPCR are differentially regulated under high-caloric conditions in human and mouse. Receptor knockdown of six receptors resulted in an impaired adipogenesis indicating their expression is essential for proper adipogenesis. The altered lipid composition was studied in more detail for two representatives, ADGRG2/GPR64 and ADGRG6/GPR126. While GPR126 is mainly involved in adipocyte differentiation, GPR64 has an additional role in mature adipocytes by regulating metabolic processes.
CONCLUSIONS
Adhesion GPCR are significantly involved in qualitative and quantitative adipocyte lipid accumulation and can control lipolysis. Factors driving adipocyte formation and function are governed by signaling pathways induced by aGPCR yielding these receptors potential targets for treating obesity.
背景
G 蛋白偶联受体（GPCR）是多种生理功能的重要调节因子，包括脂肪生成和脂肪细胞功能的调节。然而，粘附 GPCR（aGPCR）及其在脂肪组织中的作用尚未得到充分研究。鉴于肥胖治疗对新型靶点的需求，我们对该神秘 GPCR 家族在脂肪生成和成熟脂肪细胞中的表达和功能进行了全面研究。
方法
通过重新分析 RNA-Seq 数据并在低脂肪和高脂肪条件下对不同小鼠和人脂肪组织进行 qPCR，确定所有 aGPCR 代表的表达。通过 siRNA 介导的该受体类别的所有表达成员的敲低，研究 aGPCR 表达对脂肪细胞分化和脂质积累的影响。通过质谱和生化方法（脂肪分解、葡萄糖摄取、脂联素分泌）分析缺乏选定 aGPCR 的成熟脂肪细胞的生物学特征和功能。
结果
在内脏和皮下脂肪组织中，有十多个 aGPCR 显著表达，在人和小鼠中，高卡路里条件下，有几个 aGPCR 表达水平存在差异。六种受体的受体敲低导致脂肪生成受损，表明其表达对于正常的脂肪生成是必需的。对两个代表，ADGRG2/GPR64 和 ADGRG6/GPR126 的改变的脂质组成进行了更详细的研究。虽然 GPR126 主要参与脂肪细胞分化，但 GPR64 在成熟脂肪细胞中通过调节代谢过程发挥额外作用。
结论
粘附 GPCR 显著参与定性和定量的脂肪细胞脂质积累，并可控制脂肪分解。驱动脂肪细胞形成和功能的因素受 aGPCR 诱导的信号通路控制，这些受体成为治疗肥胖的潜在靶点。
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