Exercise does not Attenuate Increased Fatty Acid Metabolism in Ex Vivo Diabetic Hearts

Abstract

Diabetes mellitus produces an altered metabolic phenotype in the heart, with increased fatty acid oxidation and decreased glucose metabolism. This study determined whether regular exercise training could attenuate the consequences of enhanced cardiac fatty acid (FA) oxidation in streptozotocin-injected type 1 diabetic mice (T1D). Control (CD-1) and diabetic mice were exercised (EX) by running for 60 min/d, 5 d/wk for 6 wk at low-moderate intensity. Non-exercised sedentary (SED) groups were also studied. Hearts from T1D and control mice at 12 weeks of age were subjected to a 60-min working heart perfusion with glucose and palmitate. Oxidation of radiolabeled palmitate (complexed to albumin) was measured (μmol/min/g dry weight) along with parameters of contractile function. Diabetic mice exhibited hyperglycemia compared to CD-1 controls (P<0.01). Importantly, EX T1D group showed a significant 12% reduction in plasma glucose levels compared to T1D SED mice (41.4 vs 50.3 mM). Hearts from CD-1 and T1D groups showed no changes with exercise for any of the measured parameters of contractile function. Palmitate oxidation was increased by nearly 2-fold in T1D SED hearts compared to CD-1 SED hearts (0.72±0.12 vs 0.40±0.05 μmol/min/g dry weight). However, steady-state rates of palmitate oxidation were not significantly different between T1D SED and T1D EX hearts (0.72±0.12 vs 0.63±0.08). These results suggest fatty acid oxidation rates during perfusion, although significantly elevated in the diabetic heart, are not altered by exercise. As well 6 weeks of low-moderate exercise is not enough to improve diabetic cardiac function. However, lower blood glucose levels in T1D EX mice suggest a beneficial effect of exercise on whole-body glucose utilization. Supported by CIHR (DS).