title: Peroxisome proliferator-activated receptor β/δ activation in adult hearts facilitates mitochondrial function and cardiac performance under pressure-overload condition.
abstract: Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is an essential transcription factor in myocardial metabolism. This study aims to investigate the effects of PPARβ/δ activation in the adult heart on mitochondrial biology and oxidative metabolism under normal and pressure-overload conditions. We have investigated the effects of cardiac constitutively active PPARβ/δ in adult mice using a tamoxifen-inducible transgenic approach with Cre-LoxP recombination. The expression of PPARβ/δ mRNA and protein in cardiomyocytes of adult mice was substantially increased after short-term induction. In these mice, the cardiac expression of key factors involved in mitochondrial biogenesis, such as PPARγ coactivator-1, endogenous antioxidants Cu/Zn superoxide dismutase, and catalase, fatty acid, and glucose metabolism, such as carnitine palmitoyltransferase Ib, carnitine palmitoyltransferase II, and glucose transporter 4, were upregulated. Subsequently, myocardial oxidative metabolism was elevated concomitant with an increased mitochondrial DNA copy number and an enhanced cardiac performance. Moreover, activation of PPARβ/δ in the adult heart improved cardiac function and resisted progression to pathological development in mechanical stress condition. We conclude that PPARβ/δ activation in the adult heart will promote cardiac performance along with transcriptional upregulation of mitochondrial biogenesis and defense, as well as oxidative metabolism at basal and pressure-overload conditions.
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294-3360, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Peiyong
authors.initials: P
authors.lastname: Wang
authors.forename: Jinwen
authors.initials: J
authors.lastname: Luo
authors.forename: Yao
authors.initials: Y
authors.lastname: Huang
authors.forename: Lan
authors.initials: L
authors.lastname: He
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.forename: Qingbao
authors.initials: Q
authors.lastname: Li
authors.forename: Sijie
authors.initials: S
authors.lastname: Wu
authors.forename: Olga
authors.initials: O
authors.lastname: Zhelyabovska
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D015870:Gene Expression; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008929:Mitochondria, Heart / Q000378:metabolism / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism*; D048068:PPAR-beta / Q000235:genetics / Q000378:metabolism*; D025221:Phosphofructokinases / Q000235:genetics / Q000378:metabolism; D011312:Pressure; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D047494:PPAR delta; D048068:PPAR-beta; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse; D002374:Catalase; D013482:Superoxide Dismutase; D002334:Carnitine O-Palmitoyltransferase; D025221:Phosphofructokinases