Research ArticleMetabolism

TRIF-dependent Toll-like receptor signaling suppresses Scd1 transcription in hepatocytes and prevents diet-induced hepatic steatosis

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Science Signaling  08 Aug 2017:
Vol. 10, Issue 491, eaal3336
DOI: 10.1126/scisignal.aal3336

TRIF against fatty liver

Viral detection by TLR pathways triggers inflammatory responses, which generally aggravate metabolic diseases. However, Chen et al. found that the TLR signaling adaptor TRIF in hepatocytes, rather than myeloid cells, limited diet-induced hepatic steatosis in mice. TRIF activation downstream of TLR3 led to the transcriptional suppression of Scd1, which encodes a key lipogenic enzyme. Viral RNA and mimetics activate TLR3, and application of RNA generated by adipose tissue prevented the increase in SCD1 abundance and the enhanced triglyceride accumulation that normally occurs in hepatocytes exposed to palmitic acid, a saturated fatty acid that is enriched in high-fat diets. The authors note that the hepatitis C virus co-opts host lipogenesis to ensure its replication and that TRIF-mediated suppression of Scd1 transcription may therefore serve to limit viral infection of hepatocytes.

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