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论文题目: Deletion of Macrophage Mineralocorticoid Receptor Protects Hepatic Steatosis and Insulin Resistance Through ER/HGF/Met Pathway
英文论文题目: Deletion of Macrophage Mineralocorticoid Receptor Protects Hepatic Steatosis and Insulin Resistance Through ER/HGF/Met Pathway
第一作者: Zhang, YY; Li, C; Yao, GF; Du, LJ; Liu, Y; Zheng, XJ; Yan, S; Sun, JY; Liu, Y; Liu, MZ; Zhang, XR; Wei, G; Tong, WX; Chen, XB; Wu, Y; Sun, SY; Liu, SL; Ding, QR; Yu, Y; Yin, HY; Duan, SZ
英文第一作者: Zhang, YY; Li, C; Yao, GF; Du, LJ; Liu, Y; Zheng, XJ; Yan, S; Sun, JY; Liu, Y; Liu, MZ; Zhang, XR; Wei, G; Tong, WX; Chen, XB; Wu, Y; Sun, SY; Liu, SL; Ding, QR; Yu, Y; Yin, HY; Duan, SZ
联系作者: Duan, SZ (reprint author), Shanghai Jiao Tong Univ, Shanghai Res Inst Stomatol, Peoples Hosp 9, Lab Oral Microbiol,Sch Stomatol,Sch Med, Shanghai, Peoples R China.
英文联系作者: Duan, SZ (reprint author), Shanghai Jiao Tong Univ, Shanghai Res Inst Stomatol, Peoples Hosp 9, Lab Oral Microbiol,Sch Stomatol,Sch Med, Shanghai, Peoples R China.
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发表年度: 2017
卷: 66
期: 6
页码: 1535-1547
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.
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.
刊物名称: DIABETES
英文刊物名称: DIABETES
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学科: Endocrinology & Metabolism
英文学科: Endocrinology & Metabolism
影响因子: 8.684
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论文类别: Article
英文论文类别: Article
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