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学科主题: 临床医学
题名:
FAM3A Activates PI3K p110 alpha/Akt Signaling to Ameliorate Hepatic Gluconeogenesis and Lipogenesis
作者: Wang, Chunjiong1; Chi, Yujing2,3; Li, Jing4; Miao, Yifei1; Li, Sha1; Su, Wen1; Jia, Shi1; Chen, Zhenzhen1; Du, Shengnan1; Zhang, Xiaoyan1; Zhou, Yunfeng1; Wu, Wenhan5; Zhu, Mingyan6; Wang, Zhiwei6; Yang, Huaqian7; Xu, Guoheng1; Wang, Shiqiang7; Yang, Jichun1; Guan, Youfei1,8
刊名: HEPATOLOGY
发表日期: 2014-05-01
DOI: 10.1002/hep.26945
卷: 59, 期:5, 页:1779-1790
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Gastroenterology & Hepatology
研究领域[WOS]: Gastroenterology & Hepatology
关键词[WOS]: PANCREATIC-DERIVED FACTOR ; HIGH-FAT DIET ; BETA-CELLS ; INSULIN-RESISTANCE ; FACTOR PANDER ; TARGETED DISRUPTION ; LIPID-METABOLISM ; RECEPTOR-GAMMA ; MICE ; EXPRESSION
英文摘要:

FAM3A belongs to a novel cytokine-like gene family, and its physiological role remains largely unknown. In our study, we found a marked reduction of FAM3A expression in the livers of db/db and high-fat diet (HFD)-induced diabetic mice. Hepatic overexpression of FAM3A markedly attenuated hyperglycemia, insulin resistance, and fatty liver with increased Akt (pAkt) signaling and repressed gluconeogenesis and lipogenesis in the livers of those mice. In contrast, small interfering RNA (siRNA)-mediated knockdown of hepatic FAM3A resulted in hyperglycemia with reduced pAkt levels and increased gluconeogenesis and lipogenesis in the livers of C57BL/6 mice. In vitro study revealed that FAM3A was mainly localized in the mitochondria, where it increases adenosine triphosphate (ATP) production and secretion in cultured hepatocytes. FAM3A activated Akt through the p110 catalytic subunit of PI3K in an insulin-independent manner. Blockade of P2 ATP receptors or downstream phospholipase C (PLC) and IP3R and removal of medium calcium all significantly reduced FAM3A-induced increase in cytosolic free Ca2+ levels and attenuated FAM3A-mediated PI3K/Akt activation. Moreover, FAM3A-induced Akt activation was completely abolished by the inhibition of calmodulin (CaM). Conclusion: FAM3A plays crucial roles in the regulation of glucose and lipid metabolism in the liver, where it activates the PI3K-Akt signaling pathway by way of a Ca2+/CaM-dependent mechanism. Up-regulating hepatic FAM3A expression may represent an attractive means for the treatment of insulin resistance, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD).

语种: 英语
所属项目编号: 2012CB517504/2009CB941603/2010CB912503 ; 81170791/2011ZX09102/81322011 ; 7122107
项目资助者: Ministry of Science and Technology ; Natural Science Foundation ; "111 Project" of China ; Beijing Natural Science Foundation
WOS记录号: WOS:000337278400020
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65473
Appears in Collections:北京大学第二临床医学院_临床分子生物学研究所_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Key Lab Mol Cardiovasc Sci,Minist Educ, Beijing 100871, Peoples R China
2.Peking Univ, Peoples Hosp, Inst Clin Mol Biol, Beijing 100871, Peoples R China
3.Peking Univ, Peoples Hosp, Cent Lab, Beijing 100871, Peoples R China
4.Peking Univ, Peoples Hosp, Dept Gastroenterol, Beijing 100871, Peoples R China
5.Peking Univ, Hosp 1, Dept Surg, Beijing 100871, Peoples R China
6.Nantong Univ, Affiliated Hosp, Dept Surg, Nantong, Jiangsu, Peoples R China
7.Peking Univ, Coll Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China
8.Shenzhen Univ, Hlth Sci Ctr, Shenzhen Univ Diabet Ctr, Shenzhen, Peoples R China

Recommended Citation:
Wang, Chunjiong,Chi, Yujing,Li, Jing,et al. FAM3A Activates PI3K p110 alpha/Akt Signaling to Ameliorate Hepatic Gluconeogenesis and Lipogenesis[J]. HEPATOLOGY,2014,59(5):1779-1790.
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