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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism
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Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism

机译：脂联素调节对葡萄糖和脂质代谢至关重要的肝基因表达

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摘要

The effects of adiponectin on hepatic glucose and lipid metabolism at transcriptional level are largely unknown. We profiled hepatic gene expression in adiponectin knockout (KO) and wild-type (WT) mice by RNA sequencing. Compared with WT mice, adiponectin KO mice fed a chow diet exhibited decreased mRNA expression of rate-limiting enzymes in several important glucose and lipid metabolic pathways, including glycolysis, tricarboxylic acid cycle, fatty-acid activation and synthesis, triglyceride synthesis, and cholesterol synthesis. In addition, binding of the transcription factor Hnf4a to DNAs encoding several key metabolic enzymes was reduced in KO mice, suggesting that adiponectin might regulate hepatic gene expression via Hnf4a. Phenotypically, adiponectin KO mice possessed smaller epididymal fat pads and showed reduced body weight compared with WT mice. When fed a high-fat diet, adiponectin KO mice showed significantly reduced lipid accumulation in the liver. These lipogenic defects are consistent with the down-regulation of lipogenic genes in the KO mice.
机译：脂联素在转录水平上对肝葡萄糖和脂质代谢的影响尚不清楚。我们通过RNA测序分析了脂联素基因敲除（KO）和野生型（WT）小鼠肝基因表达。与野生型小鼠相比，饲喂高脂饮食的脂联素KO小鼠在几种重要的葡萄糖和脂质代谢途径（包括糖酵解，三羧酸循环，脂肪酸活化和合成，甘油三酸酯合成和胆固醇合成）中显示限速酶的mRNA表达降低。 。此外，转录因子Hnf4a与编码几种关键代谢酶的DNA的结合在KO小鼠中减少了，这表明脂联素可能通过Hnf4a调节肝基因表达。从表型上看，与WT小鼠相比，脂联素KO小鼠具有较小的附睾脂肪垫，并且体重减轻。当饲喂高脂饮食时，脂联素KO小鼠显示出肝脏中脂质蓄积的明显减少。这些生脂缺陷与KO小鼠中的生脂基因的下调一致。

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  • 作者

    Qingqing Liu; Bingbing Yuan; Kinyui Alice Lo; Heide Christine Patterson; Yutong Sun; Harvey F. Lodish;

  • 作者单位

    Whitehead Institute for Biomedical Research, Cambridge, MA 02142;

    Whitehead Institute for Biomedical Research, Cambridge, MA 02142;

    Whitehead Institute for Biomedical Research, Cambridge, MA 02142,Department of Biological Engineering, Massachusetts Institute of Technology,Cambridge, MA 02139;

    Whitehead Institute for Biomedical Research, Cambridge, MA 02142,Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115,lnstitut fuer Klinische Chemie und Pathobiochemie,Klinikum Rechts der Isar, Technische Universitaet Muenchen, 81675 Munich, Germany;

    Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030;

    Whitehead Institute for Biomedical Research, Cambridge, MA 02142,Department of Biological Engineering, Massachusetts Institute of Technology,Cambridge, MA 02139;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    hepatic metabolism; lipogenesis; transcriptional regulation;

    机译：肝代谢脂肪生成转录调控;

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