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CREBH-FGF21 axis improves hepatic steatosis by suppressing adipose tissue lipolysis
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CREBH-FGF21 axis improves hepatic steatosis by suppressing adipose tissue lipolysis
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Journal Article
CREBH-FGF21 axis improves hepatic steatosis by suppressing adipose tissue lipolysis
2016
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 64/60
/ 82/1
/ 82/51
/ 96/106
/ 96/109
/ Body fat
/ Chair Nutrition Metabolism and Genomics
/ Fasting
/ Genomics
/ Glucose
/ Glycerol
/ HNE Nutrition, Metabolism and Genomics
/ HNE Voeding, Metabolisme en Genomics
/ Humanities and Social Sciences
/ Kinases
/ Lipids
/ Liver
/ Medicine
/ Nutrition, Metabolism and Genomics
/ Plasma
/ Proteins
/ Science
/ VLAG
