Elevated Leptin and Triglyceride are Associated with Enhanced Mitochondrial Function Despite Ceramide Accumulation

Abstract

Accumulation of lipid and ceramide in the heart has been proposed to be a causative factor in mitochondrial dysfunction and decreased electron transport chain (ETC) activity. We hypothesized that a high saturated fat diet (SAT) would increase ceramide and inhibit mitochondrial respiration and ETC complex activity. Heart failure (HF) was induced by coronary artery ligation. HF rats were fed normal (10% kcal fat, HF) or SAT diet (60% kcal saturated fat, HF SAT) for 8 weeks. Sham rats (SHAM) were fed normal chow. Mitochondria were isolated from the left ventricle and respiration and ETC complex activities were assessed. Although myocardial ceramide was increased in HF SAT compared to SHAM and HF (5.55 ± 0.96, 3.16 ± 0.48 and 2.59 ± 0.47 nmol/gww respectively), state 3 respiration using glutamate was elevated in HF SAT compared to HF (206 ± 11 and 155 ± 11 nAO·min−1·mg−1). Activities of ETC complexes II and IV were elevated in HF SAT compared to SHAM and HF. Plasma and tissue triglycerides were elevated in HF SAT. Additionally, plasma leptin was elevated in HF SAT compared to SHAM and HF (1527 ± 243, 518 ± 140, 656 ± 183 pg/mL, respectively), though plasma insulin was not different. In conclusion, the absence of a lipotoxic effect of ceramide on mitochondrial respiration and ETC activity in HF SAT may be accounted for by a cardioprotective effect of elevated plasma leptin. (Grant # NIH HL-081857 & AHA SDG 0535361N)