title: 5'-AMP Activated Protein Kinase is Involved in the Regulation of Myocardial β-Oxidative Capacity in Mice.
abstract: 5'-adenosine monophosphate-activated protein kinase (AMPK) is considered central in regulation of energy status and substrate utilization within cells. In heart failure the energetic state is compromised and substrate metabolism is altered. We hypothesized that this could be linked to changes in AMPK activity and we therefore investigated mitochondrial oxidative phosphorylation capacity from the oxidation of long- and medium-chain fatty acids (LCFA and MCFA) in cardiomyocytes from young and old mice expressing a dominant negative AMPKα2 (AMPKα2-KD) construct and their wildtype (WT) littermates. We found a 35-45% (P < 0.05) lower mitochondrial capacity for oxidizing MCFA in AMPKα2-KD of both age-groups, compared to WT. This coincided with marked decreases in protein expression (19/29%, P < 0.05) and activity (14/21%, P < 0.05) of 3-hydroxyacyl-CoA-dehydrogenase (HAD), in young and old AMPKα2-KD mice, respectively, compared to WT. Maximal LCFA oxidation capacity was similar in AMPKα2-KD and WT mice independently of age implying that LCFA-transport into the mitochondria was unaffected by loss of AMPK activity or progressing age. Expression of regulatory proteins of glycolysis and glycogen breakdown showed equivocal effects of age and genotype. These results illustrate that AMPK is necessary for normal mitochondrial function in the heart and that decreased AMPK activity may lead to an altered energetic state as a consequence of reduced capacity to oxidize MCFA. We did not identify any clear aging effects on mitochondrial function.
authors.affiliation: Xlab, Faculty of Health Sciences, Department of Biomedical Sciences, Center for Healthy Aging, University of Copenhagen Copenhagen, Denmark.
authors.forename: Nis
authors.initials: N
authors.lastname: Stride
authors.forename: Steen
authors.initials: S
authors.lastname: Larsen
authors.forename: Jonas Thue
authors.initials: JT
authors.lastname: Treebak
authors.forename: Christina Neigaard
authors.initials: CN
authors.lastname: Hansen
authors.forename: Martin
authors.initials: M
authors.lastname: Hey-Mogensen
authors.forename: Tobias
authors.initials: T
authors.lastname: Speerschneider
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Jensen
authors.forename: Jacob
authors.initials: J
authors.lastname: Jeppesen
authors.forename: Jørgen F P
authors.initials: JF
authors.lastname: Wojtaszewski
authors.forename: Erik A
authors.initials: EA
authors.lastname: Richter
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.forename: Flemming
authors.initials: F
authors.lastname: Dela