Fatty acid metabolism is enhanced in type 2 diabetic hearts

• Published in: Biochimica et biophysica acta 2005-05, Vol.1734 (2), p.112-126
• Main Authors: Carley, Andrew N., Severson, David L.
• Format: Article
• Language: English
• Subjects: Animals; Diabetes and cardiac metabolism; Diabetes Mellitus, Type 2 - metabolism; Disease Models, Animal; Fatty acid metabolism; Fatty Acids - metabolism; Humans; Mice; Mice, Obese; Mitochondria - metabolism; Myocardium - metabolism; Obesity - metabolism; Oxidation-Reduction; Rats; Rats, Zucker
• ISSN: 1388-1981; 0006-3002; 1879-2618
• DOI: 10.1016/j.bbalip.2005.03.005

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-α. 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.