title: Fatty acid metabolism is enhanced in type 2 diabetic hearts.
abstract: The metabolic phenotype of hearts has been investigated using rodent models of type 2 diabetes which exhibit obesity and insulin resistance: db/db and ob/ob mice, and Zucker fatty and ZDF rats. In general, cardiac fatty acid (FA) utilization is enhanced in type 2 diabetic hearts, with increased rates of FA oxidation (db/db, ob/ob and ZDF models) and increased FA esterification into cellular triacylglycerols (db/db hearts). Hearts from db/db and ob/ob mice and ZDF rat hearts all have elevated levels of myocardial triacylglycerols, consistent with enhanced FA utilization. A number of mechanisms may be responsible for enhanced FA utilization in type 2 diabetic hearts: (i) increased FA uptake into cardiac myocytes and into mitochondria; (ii) altered mitochondrial function, with up-regulation of uncoupling proteins; and (iii) stimulation of peroxisome proliferator-activated receptor-alpha. Enhanced cardiac FA utilization in rodent type 2 diabetic models is associated with reduced cardiac contractile function, perhaps as a consequence of lipotoxicity and/or reduced cardiac efficiency. Similar results have been obtained with human type 2 diabetic hearts, suggesting that pharmacological interventions that can reduce cardiac FA utilization may have beneficial effects on contractile function.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Carley
authors.forename: David L
authors.initials: DL
authors.lastname: Severson
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008820:Mice, Obese; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011924:Rats, Zucker
chemical_list: D005227:Fatty Acids