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Title: Fenofibrate, a peroxisome proliferator-activated receptor α ligand, prevents abnormal liver function induced by a fasting–refeeding process

Highlights: •A fasting–refeeding high fat diet (HDF) model mimics irregular eating habit. •A fasting–refeeding HFD induces liver ballooning injury. •A fasting–refeeding HDF process elicits hepatic triglyceride accumulation. •Fenofibrate, PPARα ligand, prevents liver damage induced by refeeding HFD. -- Abstract: Fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, is an anti-hyperlipidemic agent that has been widely used in the treatment of dyslipidemia. In this study, we examined the effect of fenofibrate on liver damage caused by refeeding a high-fat diet (HFD) in mice after 24 h fasting. Here, we showed that refeeding HFD after fasting causes liver damage in mice determined by liver morphology and liver cell death. A detailed analysis revealed that hepatic lipid droplet formation is enhanced and triglyceride levels in liver are increased by refeeding HFD after starvation for 24 h. Also, NF-κB is activated and consequently induces the expression of TNF-α, IL1-β, COX-2, and NOS2. However, treating with fenofibrate attenuates the liver damage and triglyceride accumulation caused by the fasting–refeeding HFD process. Fenofibrate reduces the expression of NF-κB target genes but induces genes for peroxisomal fatty acid oxidation, peroxisome biogenesis and mitochondrial fatty acid oxidation. These results strongly suggest that the treatment of fenofibrate ameliorates the livermore » damage induced by fasting–refeeding HFD, possibly through the activation of fatty acid oxidation.« less
Authors:
; ; ; ; ;  [1] ;  [1] ;  [2] ;  [1] ;  [1] ;  [2] ;  [1] ;  [1]
  1. Center for Metabolic Function Regulation, and Department of Microbiology, School of Medicine, Wonkwang University, Iksan (Korea, Republic of)
  2. (Korea, Republic of)
Publication Date:
OSTI Identifier:
22242220
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 442; Journal Issue: 1-2; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARBOXYLIC ACIDS; DAMAGE; DEATH; DIET; DROPLETS; FASTING; FATS; INJURIES; LIGANDS; LIVER; LIVER CELLS; MICE; MITOCHONDRIA; MORPHOLOGY; OXIDATION; RECEPTORS; TRIGLYCERIDES