What is the clinical evidence from this study?

Study design: Other. Population: Diabetes. Intervention: Diabetic condition (streptozotocin treatment) vs. Normal rats. Primary outcome: Triacylglycerol (TAG) turnover rate in high-substrate group (nmol.min(-1).g(-1) dry wt) (p=<0.001).

October 19, 2005

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

Q: What are the key findings of this study?

Diabetic rat hearts exhibited significantly greater triacylglycerol turnover rates compared to normal hearts under high-substrate conditions (820 vs 190 nmol/min/g dry wt; P<0.001).

Key Result

Diabetic rat hearts exhibited significantly greater triacylglycerol turnover rates compared to normal hearts under high-substrate conditions (820 vs 190 nmol/min/g dry wt; P<0.001).

Structured PICO

Population

Isolated beating hearts from diabetic rats (streptozotocin treatment) and normal rats

Intervention

Perfusion with physiological (0.5 mM palmitate, 5 mM glucose) or elevated substrate levels (1.2 mM palmitate, 11 mM glucose) containing [2,4,6,8,10,12,14,16-(13)C(8)]palmitate

Comparator

Hearts from normal rats perfused under the same conditions

Outcome

Triacylglycerol (TAG) storage and turnover rates measured by dynamic mode (13)C-NMR spectroscopysurrogate

Diabetic rat hearts exhibit accelerated triacylglycerol turnover and evidence of compartmentalized lipid storage compared to normal hearts.

Main Result

Absolute Event Rate: 820% vs 190%

p-value: p=<0.001

Abstract

Triacylglycerol (TAG) storage and turnover rates in the intact, beating rat heart were determined for the first time using dynamic mode (13)C- 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-(13)C(8)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 >or=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(-1) dry wt; P< 0.001) and TAG content (DR 78 +/-10, NR 32+/- 4 micromol/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 micromol/g dry wt; not significant (NS). Consistent with exponential enrichment data, (13)C 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.

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