title: Improvement of myocardial lipid accumulation and prevention of PGC-1α             induction by fenofibrate.
abstract: We recently demonstrated that fenofibrate induces the activities of citrate synthase and NADH oxidase in cardiac mitochondria. To further determine the molecular mechanisms underlying fenofibrate action, 8-week-old mice were administered fenofibrate (100 mg/kg/day) for 7 and 14 days, and the expression of genes involved in cardiac mitochondrial function, such as nuclear respiratory factor 1 transcript variant 2 (NRF-1-L) and 6 (NRF-1-S), mitochondrial outer membrane protein 40 (Tom40), lipoic acid synthetase (Lias), cytochrome b, medium-chain acyl-coenzyme A dehydrogenase (MCAD) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) was determined. Expression of PGC-1α, a key regulator of the entire fatty acid oxidation system, was significantly downregulated after 14 days of fenofibrate administration. Moreover, ventricular triglycerides were also accumulated following 14 days of fenofibrate administration. Thus, fenofibrate functions to improve myocardial lipid accumulation and to prevent PGC-1α induction, which is crucial for understanding the molecular mechanisms underlying fenofibrate action on the heart.
authors.affiliation: Department of Biochemistry and Molecular Biology, Zhengzhou University, Zhengzhou City, Henan, People's Republic of China.
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Li
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Yao
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhang
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Wang
authors.forename: Tian-Qi
authors.initials: TQ
authors.lastname: Wang
authors.forename: Cheng-Juan
authors.initials: CJ
authors.lastname: Xiong
authors.forename: Yue-Bai
authors.initials: YB
authors.lastname: Li
authors.forename: Ming-Xi
authors.initials: MX
authors.lastname: Zang
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D045303:Cytochromes b / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005227:Fatty Acids / Q000378:metabolism; D011345:Fenofibrate / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D051265:NF-E2-Related Factor 1 / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D013466:Sulfurtransferases / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D000960:Hypolipidemic Agents; D051265:NF-E2-Related Factor 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D014280:Triglycerides; D045303:Cytochromes b; D042964:Acyl-CoA Dehydrogenase; D013466:Sulfurtransferases; C116435:lipoic acid synthase; D011345:Fenofibrate