Dietary linoleate preserves cardiolipin and attenuates mitochondrial dysfunction in the failing rat heart

Cardiolipin (CL) is a tetra-acyl phospholipid that provides structural and functional support to several proteins in the inner mitochondrial membrane. The majority of CL in the healthy mammalian heart contains four linoleic acid acyl chains (L4CL). A selective loss of L4CL is associated with mitochondrial dysfunction and heart failure in humans and animal models. We examined whether supplementing the diet with linoleic acid would preserve cardiac L4CL and attenuate mitochondrial dysfunction and contractile failure in rats with hypertensive heart failure. Male spontaneously hypertensive heart failure rats (21 months of age) were administered diets supplemented with high-linoleate safflower oil (HLSO) or lard (10 w/w; 28 kilocalorie fat) or without supplemental fat (control) for 4 weeks. HLSO preserved L4CL and total CL to 90 of non-failing levels (vs. 6175 in control and lard groups), and attenuated 1722 decreases in state 3 mitochondrial respiration observed in the control and lard groups (P 0.05). Left ventricular fractional shortening was significantly higher in HLSO vs. control (33 2 vs. 29 2, P 0.05), while plasma insulin levels were lower (5.4 1.1 vs. 9.1 2.3 ng/mL; P 0.05), with no significant effect of lard supplementation. HLSO also increased serum concentrations of several eicosanoid species compared with control and lard diets, but had no effect on plasma glucose or blood pressure. Moderate consumption of HLSO preserves CL and mitochondrial function in the failing heart and may be a useful adjuvant therapy for this condition.