期刊
SCIENCE SIGNALING
卷 10, 期 491, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.aal3336
关键词
-
资金
- Research Centre of Heart, Brain, Hormone and Healthy Aging of the University of Hong Kong [200007252]
- National Key Basic Research Development Program 973 [2015CB553603]
- Hong Kong Research Grants Council/Collaborative Research Fund [C7055-14G]
- University of Hong Kong
Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that ranges in severity from hepatic steatosis to steatohepatitis, the latter of which is a major predisposing factor for liver cirrhosis and cancer. Toll-like receptor (TLR) signaling, which is critical for innate immunity, is generally believed to aggravate disease progression by inducing inflammation. Unexpectedly, we found that deficiency in TIR domain-containing adaptor-inducing interferon-beta (TRIF), a cytosolic adaptor that transduces some TLR signals, worsened hepatic steatosis induced by a high-fat diet (HFD) and that such exacerbation was independent of myeloid cells. The aggravated steatosis in Trif(-/-) mice was due to the increased hepatocyte transcription of the gene encoding stearoyl-coenzyme A (CoA) desaturase 1 (SCD1), the rate-limiting enzyme for lipogenesis. Activation of the TRIF pathway by polyinosinic: polycytidylic acid [poly(I:C)] suppressed the increase in SCD1 abundance induced by palmitic acid or an HFD and subsequently prevented lipid accumulation in hepatocytes. Interferon regulatory factor 3 (IRF3), a transcriptional regulator downstream of TRIF, acted as a transcriptional suppressor by directly binding to the Scd1 promoter. These results suggest an unconventional metabolic function for TLR/TRIF signaling that should be taken into consideration when seeking to pharmacologically inhibit this pathway.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据