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本文引用的文献

1
Activation of serum response element by D2 dopamine receptor is governed by Gbetagamma-mediated MAPK and Rho pathways and regulated by RGS proteins.D2多巴胺受体对血清反应元件的激活受Gβγ介导的丝裂原活化蛋白激酶（MAPK）和Rho途径调控，并受调节G蛋白信号的蛋白质（RGS蛋白）调节。
Pharmacology. 2007;79(2):114-21. doi: 10.1159/000098097. Epub 2006 Dec 18.
2
Sympathetic system activity in obesity and metabolic syndrome.肥胖与代谢综合征中的交感神经系统活动。
Ann N Y Acad Sci. 2006 Nov;1083:129-52. doi: 10.1196/annals.1367.010.
3
Identification of small-molecule inhibitors of RGS4 using a high-throughput flow cytometry protein interaction assay.使用高通量流式细胞术蛋白质相互作用测定法鉴定RGS4的小分子抑制剂。
Mol Pharmacol. 2007 Jan;71(1):169-75. doi: 10.1124/mol.106.028670. Epub 2006 Sep 29.
4
Hepatic glucose production is more sensitive to insulin-mediated inhibition than hepatic VLDL-triglyceride production.肝脏葡萄糖生成对胰岛素介导的抑制作用比肝脏极低密度脂蛋白甘油三酯生成更为敏感。
Am J Physiol Endocrinol Metab. 2006 Dec;291(6):E1360-4. doi: 10.1152/ajpendo.00188.2006. Epub 2006 Jul 18.
5
Molecular genetic studies of schizophrenia.精神分裂症的分子遗传学研究。
Eur J Hum Genet. 2006 Jun;14(6):669-80. doi: 10.1038/sj.ejhg.5201571.
6
Adipose tissue lipolysis as a metabolic pathway to define pharmacological strategies against obesity and the metabolic syndrome.脂肪组织脂解作用作为一种代谢途径，用于确定对抗肥胖和代谢综合征的药理学策略。
Pharmacol Res. 2006 Jun;53(6):482-91. doi: 10.1016/j.phrs.2006.03.009. Epub 2006 Mar 27.
7
Human fat cell lipolysis: biochemistry, regulation and clinical role.人类脂肪细胞的脂肪分解：生物化学、调节及临床作用
Best Pract Res Clin Endocrinol Metab. 2005 Dec;19(4):471-82. doi: 10.1016/j.beem.2005.07.004.
8
Generation and characterization of Rgs4 mutant mice.Rgs4突变小鼠的产生与特性分析
Mol Cell Biol. 2005 May;25(10):4221-8. doi: 10.1128/MCB.25.10.4221-4228.2005.
9
Multi-tasking RGS proteins in the heart: the next therapeutic target?心脏中的多任务RGS蛋白：下一个治疗靶点？
Circ Res. 2005 Mar 4;96(4):401-11. doi: 10.1161/01.RES.0000158287.49872.4e.
10
Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase.脂肪组织中的脂肪动员由脂肪甘油三酯脂肪酶促进。
Science. 2004 Nov 19;306(5700):1383-6. doi: 10.1126/science.1100747.

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.

DOI:10.1210/en.2008-0717
PMID:18635652
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2605582/
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。