Post Infarction High Saturated Fat Feeding Does Not Exacerbate LV Dysfunction but Enhances Mitochondrial Function

Abstract

Accumulation of lipid and ceramide in the heart is associated with contractile dysfunction, and 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 exacerbate left ventricular (LV) dysfunction and decrease mitochondrial respiration and ETC complex activity. Heart failure was induced by coronary artery ligation. Rats were fed normal chow (10% kcal from fat, HF, n=8) or SAT (60% kcal from saturated fat, HF FAT, n=7) for 8 weeks. Sham rats (SHAM, n=8) were fed normal chow. LV function was assessed by echocardiography. Interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria were isolated from the LV and ETC complex activities and oxidative phosphorylation were assessed. Peak LV +/−dP/dt were decreased with HF (+4466 ± 487 and −3959 ± 396 mmHg/min) compared to SHAM (+6134 ± 526 and −5569 ± 401 mmHg/min) (p<0.05); but was not decreased in HF FAT (+5406 ± 459, −4353 ± 317). Myocardial ceramide was elevated in HF FAT compared to SHAM and HF (5.55 ± 0.96, 3.16 ± 0.48 and 2.59 ± 0.47 nmol/gww respectively). Complex IV activity was elevated in the SSM of HF FAT compared to HF. State 3 respiration was increased in HF FATcompared to HF in the SSM and IFM using palmitoyl CoA and palmitoylcarnitine as respiratory substrates. Contrary to previous findings suggesting a high SAT diet would lead to lipotoxicity, SAT enhanced mitochondrial respiration and ETC activity and did not exacerbate LV dysfunction.