title: Mechanisms responsible for enhanced fatty acid utilization by perfused hearts from type 2 diabetic db/db mice.
abstract: The aim of this study was to determine the biochemical mechanism(s) responsible for enhanced FA utilization (oxidation and esterification) by perfused hearts from type 2 diabetic db/db mice. The plasma membrane content of fatty acid transporters FAT/CD36 and FABPpm was elevated in db/db hearts. Mitochondrial mechanisms that could contribute to elevated rates of FA oxidation were also examined. Carnitine palmitoyl transferase-1 activity was unchanged in mitochondria from db/db hearts, and sensitivity to inhibition by malonyl-CoA was unchanged. Malonyl-CoA content was elevated and AMP kinase activity was decreased in db/db hearts, opposite to what would be expected in hearts exhibiting elevated rates of FA oxidation. Uncoupling protein-3 expression was unchanged in mitochondria from db/db hearts. Therefore, enhanced FA utilization in db/db hearts is most likely due to increased FA uptake caused by increased plasma membrane content of FA transporters; the mitochondrial mechanisms examined do not contribute to elevated FA oxidation observed in db/db hearts.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: A N
authors.initials: AN
authors.lastname: Carley
authors.forename: L L
authors.initials: LL
authors.lastname: Atkinson
authors.forename: A
authors.initials: A
authors.lastname: Bonen
authors.forename: M-E
authors.initials: ME
authors.lastname: Harper
authors.forename: S
authors.initials: S
authors.lastname: Kunnathu
authors.forename: G D
authors.initials: GD
authors.lastname: Lopaschuk
authors.forename: D L
authors.initials: DL
authors.lastname: Severson
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion
chemical_list: D005227:Fatty Acids