title: Fenofibrate, a peroxisome proliferator-activated receptor α ligand, prevents abnormal liver function induced by a fasting-refeeding process.
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 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.
authors.affiliation: Center for Metabolic Function Regulation, and Department of Microbiology, School of Medicine, Wonkwang University, Iksan, South Korea.
authors.forename: Joon No
authors.initials: JN
authors.lastname: Lee
authors.forename: Raghbendra Kumar
authors.initials: RK
authors.lastname: Dutta
authors.forename: Seul-Gi
authors.initials: SG
authors.lastname: Kim
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Lim
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Seong-Kyu
authors.initials: SK
authors.lastname: Choe
authors.forename: Kyeong-Won
authors.initials: KW
authors.lastname: Yoo
authors.forename: Seung Ryel
authors.initials: SR
authors.lastname: Song
authors.forename: Do-Sim
authors.initials: DS
authors.lastname: Park
authors.forename: Hong-Seob
authors.initials: HS
authors.lastname: So
authors.forename: Raekil
authors.initials: R
authors.lastname: Park
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D005215:Fasting / Q000009:adverse effects*; D005227:Fatty Acids / Q000378:metabolism; D011345:Fenofibrate / Q000008:administration & dosage*; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D008024:Ligands; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D000960:Hypolipidemic Agents; D008024:Ligands; D016328:NF-kappa B; D047493:PPAR alpha; D014280:Triglycerides; D011345:Fenofibrate
keywords: Fasting–refeeding; Fatty acid oxidation; Fenofibrate; PPARα; Triglyceride