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促卵泡生成素通过Gαi/Ca(2+)/CREB信号通路调控衰老过程中的脂肪积累与重新分布。

FSH regulates fat accumulation and redistribution in aging through the Gαi/Ca(2+)/CREB pathway.

作者信息

Liu Xin-Mei, Chan Hsiao Chang, Ding Guo-Lian, Cai Jie, Song Yang, Wang Ting-Ting, Zhang Dan, Chen Hui, Yu Mei Kuen, Wu Yan-Ting, Qu Fan, Liu Ye, Lu Yong-Chao, Adashi Eli Y, Sheng Jian-Zhong, Huang He-Feng

机构信息

International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Pathology & Pathophysiology, School of Medicine, Zhejiang University, Zhejiang, China; Shanghai Jiao Tong University - The Chinese University of Hong Kong Joint Research Center for Human Reproduction and Related Diseases, Shanghai, China.

出版信息

Aging Cell. 2015 Jun;14(3):409-20. doi: 10.1111/acel.12331. Epub 2015 Mar 6.

DOI:10.1111/acel.12331
PMID:25754247
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4406670/
Abstract

Increased fat mass and fat redistribution are commonly observed in aging populations worldwide. Although decreased circulating levels of sex hormones, androgens and oestrogens have been observed, the exact mechanism of fat accumulation and redistribution during aging remains obscure. In this study, the receptor of follicle-stimulating hormone (FSH), a gonadotropin that increases sharply and persistently with aging in both males and females, is functionally expressed in human and mouse fat tissues and adipocytes. Follicle-stimulating hormone was found to promote lipid biosynthesis and lipid droplet formation; FSH could also alter the secretion of leptin and adiponectin, but not hyperplasia, in vitro and in vivo. The effects of FSH are mediated by FSH receptors coupled to the Gαi protein; as a result, Ca(2+) influx is stimulated, cAMP-response-element-binding protein is phosphorylated, and an array of genes involved in lipid biosynthesis is activated. The present findings depict the potential of FSH receptor-mediated lipodystrophy of adipose tissues in aging. Our results also reveal the mechanism of fat accumulation and redistribution during aging of males and females.

摘要

全球老龄化人群中普遍存在脂肪量增加和脂肪重新分布的现象。尽管已观察到循环性激素、雄激素和雌激素水平下降，但衰老过程中脂肪积累和重新分布的确切机制仍不清楚。在这项研究中，促卵泡激素（FSH）的受体在人和小鼠脂肪组织及脂肪细胞中功能性表达，FSH是一种促性腺激素，在男性和女性中均会随着年龄增长而急剧持续升高。研究发现促卵泡激素可促进脂质生物合成和脂滴形成；在体外和体内，FSH还可改变瘦素和脂联素的分泌，但不影响增生。FSH的作用由与Gαi蛋白偶联的FSH受体介导；结果是刺激Ca(2+)内流，磷酸化环磷酸腺苷反应元件结合蛋白，并激活一系列参与脂质生物合成的基因。目前的研究结果描述了FSH受体介导的衰老过程中脂肪组织脂肪代谢障碍的可能性。我们的研究结果还揭示了男性和女性衰老过程中脂肪积累和重新分布的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95f7/4406670/3f1d62ac007c/acel0014-0409-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95f7/4406670/1e381598a75d/acel0014-0409-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95f7/4406670/83350e03e1d9/acel0014-0409-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95f7/4406670/696217fa7626/acel0014-0409-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95f7/4406670/df2f6fb7d71a/acel0014-0409-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95f7/4406670/9e068db738eb/acel0014-0409-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95f7/4406670/3f1d62ac007c/acel0014-0409-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95f7/4406670/1e381598a75d/acel0014-0409-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95f7/4406670/83350e03e1d9/acel0014-0409-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95f7/4406670/696217fa7626/acel0014-0409-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95f7/4406670/df2f6fb7d71a/acel0014-0409-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95f7/4406670/9e068db738eb/acel0014-0409-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95f7/4406670/3f1d62ac007c/acel0014-0409-f6.jpg

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