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

• Published in: Biochemical and biophysical research communications Vol. 442; no. 1-2; pp. 22 - 27
• Main Authors: Lee, Joon No, Dutta, Raghbendra Kumar, Kim, Seul-Gi, Lim, Jae-Young, Kim, Se-Jin, Choe, Seong-Kyu, Yoo, Kyeong-Won, Song, Seung Ryel, Park, Do-Sim, So, Hong-Seob, Park, Raekil
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.12.2013
• Subjects: 60 APPLIED LIFE SCIENCES; Active Transport, Cell Nucleus; Animals; CARBOXYLIC ACIDS; Cell Nucleus - metabolism; DAMAGE; DEATH; DIET; Diet, High-Fat - adverse effects; DROPLETS; FASTING; Fasting - adverse effects; Fasting–refeeding; FATS; Fatty acid oxidation; Fatty Acids - metabolism; Fenofibrate; Fenofibrate - administration & dosage; Hypolipidemic Agents - administration & dosage; INJURIES; LIGANDS; LIVER; Liver - drug effects; Liver - metabolism; Liver - pathology; LIVER CELLS; MICE; MITOCHONDRIA; MORPHOLOGY; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; OXIDATION; Oxidation-Reduction; PPAR alpha - metabolism; PPARα; RECEPTORS; Triglyceride; TRIGLYCERIDES; Triglycerides - metabolism; Fenofibrate; Fatty acid oxidation; PPARα; Triglyceride; Fasting–refeeding
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.10.140

•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. 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 24h 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 24h. 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 liver damage induced by fasting–refeeding HFD, possibly through the activation of fatty acid oxidation.