Abstract 16193: Impaired Cardiac and Skeletal Muscle Lipid Metabolism and Reduced Cardiac Fatty Acid and Triglyceride Levels in Patients With Advanced Heart Failure
BACKGROUND: Impaired lipid metabolism contributes to cardiac dysfunction and progression of heart failure (HF). Aim of this study was to evaluate pathways of lipid metabolism and changes in free fatty acid (FFA), triglyceride (TG) and fatty acyl-coA content in plasma and muscles of patients with advanced HF.
METHODS: Myocardium, rectus muscle and serum samples were collected from 10 HF patients (pts) before and after ventricular assist device (VAD) placement and 5 controls (con). FFA, fatty acyl-CoA and TG composition in myocardium, muscle and serum was measured by liquid chromatography-tandem mass spectrometry (LC/MS). Expression of genes involved in lipid metabolism was analyzed by RT-PCR.
RESULTS: HF pts showed increased circulating FFA levels (525.6±136.9 vs. 366.6±94.6 uM in con; p<0.05). In contrast, myocardial FFA levels (total and C16:1, C16, C18:1 and C18) decreased in pts with HF (1.4±0.3 vs. 2.7±0.7 umol/g in con; p<0.05). TG, the major storage form of FFA, and fatty acyl-CoA, the active form of FFA, also was reduced in myocardium from HF pts (TG: 3.5±1.8 vs. 9.2±3.7 mg/g in con, p<0.01; fatty acyl CoA: 2.0±0.4 vs. 4.8±0.4 nmol/g in con, p<0.001). After VAD implantation cardiac fatty acyl-CoA levels were no longer significantly different than controls (4.2±1.0nmol/g), while FFA and TG were not altered by VAD placement. HF was associated with reduced cardiac mRNA levels of PGC1α (5 fold, p<0.05) and ATGL (40 fold, p<0.05) without changes of CD36, DGAT1 or 2. VAD induced cardiac CD36 (1.8 fold, p<0.05) and PGC1α (2 fold, p<0.05). VAD increased skeletal muscle FFA content (C14:1, C14, C16:1, C16, C18:3, C18:2, C18:1, C18, C20:1) (total FFA: 230.5±71.7 vs. 65.4±8.9 nmol/g pre-VAD; p<0.01) consistent with improved peripheral metabolism. Further, after VAD skeletal muscle expression of CD36 (3 fold, p<0.01), CPT1 (3.6 fold, p<0.05) and PGC1α (2.4 fold, p>0.05) increased, suggesting improvement in lipid metabolism and oxidative capacity.
CONCLUSION: Abnormal myocardial and skeletal muscle lipid content in HF improves after mechanical unloading. In part, this might be due to induction of cellular oxidative capacity. These findings show that metabolic interventions in pts with HF lead to a normalization of heart and skeletal muscle lipid metabolism.
- © 2011 by American Heart Association, Inc.