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Deletion of Macrophage Mineralocorticoid Receptor Protects Hepatic Steatosis and Insulin Resistance Through ER/HGF/Met Pathway

文献类型：期刊论文

作者Zhang, Yu-Yao7,8,9; Li, Chao7,8,9; Du, Lin-Juan7,8,9; Liu, Yuan7,8,9; Zheng, Xiao-Jun7,8,9; Liu, Yan7,8; Duan, Sheng-Zhong7,8; Sun, Shuyang8; Yao, Gao-Feng9; Yan, Shuai9
刊名DIABETES
出版日期2017
卷号66期号:6页码:1535-1547
关键词myocardial infarction ischemia reperfusion late reperfusion immune response inflammatory cytokines angiogenesis cyclosporine A
ISSN号0012-1797
DOI10.2337/db16-1354
文献子类Article
英文摘要Although the importance of macrophages in nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) has been recognized, how macrophages affect hepatocytes remains elusive. Mineralocorticoid receptor (MR) has been implicated to play important roles in NAFLD and T2DM. However, cellular and molecular mechanisms are largely unknown. We report that myeloid MR knockout (MRKO) improves glucose intolerance, insulin resistance, and hepatic steatosis in obese mice. Estrogen signaling is sufficient and necessary for such improvements. Hepatic gene and protein expression suggests that MRKO reduces hepatic lipogenesis and lipid storage. In the presence of estrogen, MRKO in macrophages decreases lipid accumulation and increases insulin sensitivity of hepatocytes through hepatocyte growth factor (HGF)/Met signaling. MR directly regulates estrogen receptor 1 (Esr1 [encoding ER]) in macrophages. Knockdown of hepatic Met eliminates the beneficial effects of MRKO in female obese mice. These findings identify a novel MR/ER/HGF/Met pathway that conveys metabolic signaling from macrophages to hepatocytes in hepatic steatosis and insulin resistance and provide potential new therapeutic strategies for NAFLD and T2DM.
学科主题Endocrinology & Metabolism
WOS关键词FATTY-ACID-METABOLISM ; GROWTH-FACTOR GENE ; NONALCOHOLIC STEATOHEPATITIS ; NUTRITIONAL REGULATION ; SHOTGUN LIPIDOMICS ; BIOLOGICAL SAMPLES ; ESTROGEN-RECEPTOR ; MASS-SPECTROMETRY ; NUCLEAR RECEPTORS ; DEFICIENT MICE
语种英语
WOS记录号WOS:000401700400013
出版者AMER DIABETES ASSOC
版本出版稿
源URL[http://202.127.25.144/handle/331004/532]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Shanghai Jiao Tong Univ, Peoples Hosp 9, Dept Oral & Maxillofacial Head Neck Oncol, Sch Med, Shanghai, Peoples R China;
2.Tianjin Med Univ, Sch Basic Med Sci, Dept Pharmacol, Tianjin, Peoples R China,
3.Fudan Univ, Key Lab Breast Canc Shanghai, Inst Canc, Inst Biomed Sci, Shanghai, Peoples R China;
4.Fudan Univ, Shanghai Canc Ctr, Shanghai, Peoples R China;
5.Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA;
6.Charles R Drew Univ Med & Sci, Dept Internal Med, Div Canc Res & Training, 1621 E 120th St, Los Angeles, CA 90059 USA;
7.Shanghai Jiao Tong Univ, Shanghai Res Inst Stomatol, Peoples Hosp 9, Lab Oral Microbiol,Sch Stomatol,Sch Med, Shanghai, Peoples R China;
8.Shanghai Jiao Tong Univ, Shanghai Key Lab Stomatol, Sch Med, Shanghai, Peoples R China;
9.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai, Peoples R China;
10.Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Key Lab Computat Biol, Shanghai, Peoples R China;
推荐引用方式
GB/T 7714		 Zhang, Yu-Yao,Li, Chao,Du, Lin-Juan,et al. Deletion of Macrophage Mineralocorticoid Receptor Protects Hepatic Steatosis and Insulin Resistance Through ER/HGF/Met Pathway[J]. DIABETES,2017,66(6):1535-1547.
APA Zhang, Yu-Yao.,Li, Chao.,Du, Lin-Juan.,Liu, Yuan.,Zheng, Xiao-Jun.,...&,.(2017).Deletion of Macrophage Mineralocorticoid Receptor Protects Hepatic Steatosis and Insulin Resistance Through ER/HGF/Met Pathway.DIABETES,66(6),1535-1547.
MLA Zhang, Yu-Yao,et al."Deletion of Macrophage Mineralocorticoid Receptor Protects Hepatic Steatosis and Insulin Resistance Through ER/HGF/Met Pathway".DIABETES 66.6(2017):1535-1547.

入库方式： OAI收割

来源：上海营养与健康研究所

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