Abstract 9304: Chain Length and Saturation of Primary Dietary Fats Mediate Impaired or Preserved Triglyceride Dynamics and Contractility in Decompensated Hearts
Oxidation of long chain fatty acids (LCFA) provides approximately 70% of ATP in the heart. Alternatively, LCFAs incorporate into the endogenous lipid pool as triacylglyceride (TAG). The dynamic process of TAG turnover, a source of LCFA for beta-oxidation and nuclear receptor activation, is reduced in cardiac hypertrophy. The current study tested the hypothesis that LCFA storage kinetics are influenced by acyl chain composition by comparing incorporation of two major plasma LCFAs, palmitate (16-carbon, saturated) and oleate (18-carbon, monounsaturated), into the TAG pool of sham operated control (SHAM) and hypertrophied (HYP) rat hearts. Isolated hearts were perfused with buffer containing 5 mM glucose, 1 mM lactate and 0.4 mM of either 13C-palmitate or 13C-oleate. Sequential 13C NMR of intact hearts and endpoint LC/MS enabled quantitation of TAG dynamics. With palmitate, HYP hearts contained 48% less TAG vs SHAM (P<0.01), while oleate maintained similar TAG in HYP and SHAM. LCFA incorporation into TAG displayed two distinct kinetic components: a saturable exponential, reflecting LCFA uptake, and a linear component, reflecting TAG turnover. Time contants of the exponential uptake phase reflected similar rates of uptake of either LCFA in SHAM and HYP. However, HYP displayed reduced TAG turnover with palmitate (HYP: 46.7 +/- 12.2 nmol/gdw/min, SHAM: 84.3 +/- 4.9; P<0.01), while oleate supported similarly elevated turnover in both groups (HYP: 140.4 +/- 11.2 nmol/gdw/min, SHAM: 143.9 +/- 15.6). Work output (rate-pressure-product) was reduced simlarly in HYP with either LCFA. In contrast, oleate supported greater contractility than palmitate in HYP for both +dP/dt (25%) and -dP/dt (23%) (P<0.05), despite no differences in the contribution of either LCFA to beta-oxidation. These data demsontrate the influence of FA composition on TAG turnover in both normal and hypertrophied myocardium, with oleate being more readily incorporated into TAG than palmitate. The findings link reduced TAG turnover rates to impaired dP/dt which can be mediated by LCFA species. Furthermore, oleate confers improved lipid content and storage dynamics in comparison to palmitate in the setting of pressure-overload hypertrophy, which are linked to cardiac contractility.
- © 2012 by American Heart Association, Inc.