Accelerated triacylglycerol turnover kinetics in hearts of diabetic rats include evidence for compartmented lipid storage

Abstract

Triacylglycerol (TAG) storage and turnover rates in the intact, beating rat heart were determined for the first time using dynamic mode13C- NMR spectroscopy to elucidate profound differences between hearts from diabetic rats (DR, streptozotocin treatment) and normal rats (NR). The incorporation of [2,4,6,8,10,12,14,16-13C8]palmitate into the TAG pool was monitored in isolated hearts perfused with physiological (0.5 mM palmitate, 5 mM glucose) and elevated substrate levels (1.2 mM palmitate, 11 mM glucose) characteristic of the diabetic condition. Surprisingly, although the normal hearts were enriched at a near-linear profile for ≥2 h before exponential characterization, exponential enrichment of TAG in diabetic hearts reached steady state after only 45 min. Consequently, TAG turnover rate was determined by fitting an exponential model to enrichment data rather than conventional two-point linear analysis. In the high-substrate group, both turnover rate (DR 820 ± 330, NR 190 ± 150 nmol·min−1·g−1dry wt; P < 0.001) and [TAG] content (DR 78 ± 10, NR 32 ± 4 μmol/g dry wt; P < 0.001) were greater in the diabetic group. At lower substrate concentrations, turnover was greater in diabetics (DR 530 ± 300, NR 160 ± 30; P < 0.05). However, this could not be explained by simple mass action, because [TAG] content was similar between groups [DR 34 ± 7, NR 39 ± 9 μmol/g dry wt; not significant (NS)]. Consistent with exponential enrichment data,13C fractional enrichment of TAG was lower in diabetics (low- substrate groups: DR 4 ± 1%, NR 10 ± 4%, P < 0.05; high-substrate groups: DR 8 ± 3%, NR 14 ± 9%, NS), thereby supporting earlier speculation that TAG is compartmentalized in the diabetic heart.