TRIACYLGLYCEROL TURNOVER IN ISOLATED WORKING HEARTS OF ACUTELY DIABETIC RATS

Although myocardial triacylglycerol may be a potentially important sou rce of fatty acids for beta-oxidation in diabetes, few studies have me asured triacylglycerol turnover directly in hearts from diabetic anima ls. In this study, myocardial triacylglycerol turnover was directly me asured in isolated working hearts from streptozotocin-induced acutely diabetic rats. Hearts were initially perfused in the presence of 1.2 m M [C-14]palmitate and 11 mM glucose for 1 h (pulse) to label the endog enous lipid pools, followed by a 10-min washout perfusion. Hearts were then perfused for another hour (chase) with buffer containing 11 mM g lucose +/- 1.2 mM [H-3]palmitate. During the chase, both (CO2)-C-14 an d (H2O)-H-3 production (measures of endogenous and exogenous fatty aci d oxidation, respectively) were determined. A second series of hearts were perfused using the same protocol, except that unlabeled palmitate was used during the pulse and 11 mM [(CO2)-C-14(U),5-H-3]glucose +/- unlabeled palmitate was present during the chase. Both glycolysis ((H2 O)-H-3 pproduction) and glucose oxidation ((CO2)-C-14 production) rate s were measured in this series. Myocardial triacylglycerol levels were significantly higher in the diabetic rat hearts (77.5 +/- 4.6 vs. 33. 7 +/- 4.1 mu mol fatty acid/g dry mass in control hearts). In diabetic rat hearts chased with 1.2 mM palmitate, triacylglycerol lipolysis wa s increased, although endogenous [C-14]palmitate oxidation rates were similar to control hearts and contributed 10.1% of overall ATP product ion. The majority of fatty acids derived from triacylglycerol lipolysi s were released into the perfusate. In the absence of palmitate, both triacylglycerol lipolysis and endogenous [C-14]palmitate oxidation rat es were significantly increased in diabetic rat hearts, compared with control. Under these conditions, triacylglycerol fatty acid oxidation contributed 70% of steady-state ATP production in diabetic rat hearts, compared with 34% in control hearts. These results demonstrate that i n diabetic rat hearts myocardial triacylglycerol lipolysis is signific antly increased and can readily be used as a source of fatty acids for mitochondrial beta-oxidation.