G蛋白信号调节因子4控制脂肪酸和葡萄糖稳态。
Regulator of G protein signaling-4 controls fatty acid and glucose homeostasis.
作者信息
Iankova Irena, Chavey Carine, Clapé Cyrielle, Colomer Claude, Guérineau Nathalie C, Grillet Nicolas, Brunet Jean-François, Annicotte Jean-Sébastien, Fajas Lluis
机构信息
Institut National de la Santé et de la Recherche Médicale, Unité 834, Montpellier F-34298, France.
出版信息
Endocrinology. 2008 Nov;149(11):5706-12. doi: 10.1210/en.2008-0717. Epub 2008 Jul 17.
Abstract
Circulating free fatty acids are a reflection of the balance between lipogenesis and lipolysis that takes place mainly in adipose tissue. We found that mice deficient for regulator of G protein signaling (RGS)-4 have increased circulating catecholamines, and increased free fatty acids. Consequently, RGS4-/- mice have increased concentration of circulating free fatty acids; abnormally accumulate fatty acids in liver, resulting in liver steatosis; and show a higher degree of glucose intolerance and decreased insulin secretion in pancreas. We show in this study that RGS4 controls adipose tissue lipolysis through regulation of the secretion of catecholamines by adrenal glands. RGS4 controls the balance between adipose tissue lipolysis and lipogenesis, secondary to its role in the regulation of catecholamine secretion by adrenal glands. RGS4 therefore could be a good target for the treatment of metabolic diseases.
摘要
循环游离脂肪酸反映了主要在脂肪组织中发生的脂肪生成与脂肪分解之间的平衡。我们发现，缺乏G蛋白信号调节剂（RGS）-4的小鼠循环儿茶酚胺增加，游离脂肪酸也增加。因此，RGS4基因敲除小鼠循环游离脂肪酸浓度升高；脂肪酸在肝脏中异常蓄积，导致肝脂肪变性；并且表现出更高程度的葡萄糖不耐受以及胰腺胰岛素分泌减少。我们在本研究中表明，RGS4通过调节肾上腺儿茶酚胺的分泌来控制脂肪组织的脂肪分解。RGS4控制脂肪组织脂肪分解与脂肪生成之间的平衡，这继发于其在调节肾上腺儿茶酚胺分泌中的作用。因此，RGS4可能是治疗代谢性疾病的一个良好靶点。
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