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CREBH-FGF21 axis improves hepatic steatosis by suppressing adipose tissue lipolysis

Authors
 Jong-Gil Park  ;  Xu Xu  ;  Sungyun Cho  ;  Kyu Yeon Hur  ;  Myung-Shik Lee  ;  Sander Kersten  ;  Ann-Hwee Lee 
Citation
 SCIENTIFIC REPORTS, Vol.6 : 27938, 2016 
Journal Title
 SCIENTIFIC REPORTS 
Issue Date
2016
MeSH
Adipose Tissue/pathology* ; Animals ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Fatty Liver/pathology* ; Feedback, Physiological ; Fibroblast Growth Factors/metabolism* ; Lipolysis* ; Mice, Inbred C57BL ; Mice, Knockout
Abstract
Adipose tissue lipolysis produces glycerol and nonesterified fatty acids (NEFA) that serve as energy sources during nutrient scarcity. Adipose tissue lipolysis is tightly regulated and excessive lipolysis causes hepatic steatosis, as NEFA released from adipose tissue constitutes a major source of TG in the liver of patients with nonalcoholic fatty liver diseases. Here we show that the liver-enriched transcription factor CREBH is activated by TG accumulation and induces FGF21, which suppresses adipose tissue lipolysis, ameliorating hepatic steatosis. CREBH-deficient mice developed severe hepatic steatosis due to increased adipose tissue lipolysis, when fasted or fed a high-fat low-carbohydrate ketogenic diet. FGF21 production was impaired in CREBH-deficient mice, and adenoviral overexpression of FGF21 suppressed adipose tissue lipolysis and improved hepatic steatosis in these mice. Thus, our results uncover a negative feedback loop in which CREBH regulates NEFA flux from adipose tissue to the liver via FGF21.
Files in This Item:
T201603514.pdf Download
DOI
10.1038/srep27938
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Lee, Myung Shik(이명식) ORCID logo https://orcid.org/0000-0003-3292-1720
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/152019
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