Key result
Combined therapy with L-carnitine and fenofibrate dramatically improved the survival rate at 400 days after birth in JVS mice compared to controls.
Why the study?
Does combined therapy with fenofibrate and L-carnitine improve survival and cardiac metabolism in a murine model of systemic carnitine deficiency?
Does combined therapy with fenofibrate and L-carnitine improve survival and cardiac metabolism in a murine model of systemic carnitine deficiency?
Combined PPARalpha activation and L-carnitine supplementation rescues lipotoxic cardiomyopathy and improves survival in a murine model of systemic carnitine deficiency.
Answers are grounded in this paper and cite their sources.
Findings remain preclinical; leaves open translation of combined L-carnitine and fenofibrate to human carnitine deficiency.
OBJECTIVE: Peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily and are key regulators of fatty acid oxidation (FAO) in the heart. Systemic carnitine deficiency (SCD) causes disorders of FAO and induces hypertrophic cardiomyopathy with lipid accumulation. We hypothesized that activation of PPARalpha by fenofibrate, a PPARalpha agonist, in addition to conventional L-carnitine supplementation may exert beneficial effects on the lipotoxic cardiomyopathy in juvenile visceral steatosis (JVS) mouse, a murine model of SCD. METHODS: Both wild-type (WT) and JVS mice were fed a normal chow, 0.2% fenofibrate containing chow (FE), a 0.1% L-carnitine containing chow (CA) or a 0.1% L-carnitine + 0.2% fenofibrate containing chow (CA + FE) from 4 weeks of age. Four to 8 animals per group were used for each experiment and 9 to 11 animals per group were used for survival analysis. RESULTS: At 8 weeks of age, JVS mice exhibited marked ventricular hypertrophy, which was more attenuated by CA + FE than by CA or FE alone. CA + FE markedly reduced the high plasma and myocardial triglyceride levels and increased the low myocardial ATP content to control levels in JVS mice. In JVS mice, myocardial 1,2-diacylglycerol (DAG) was significantly increased and showed a distinct fatty acid composition with elevation of 18:1(n-7,9) and 18:2(n-6) fatty acids compared with that in WT mice. CA + FE significantly altered the fatty acid composition of DAG and inhibited the membrane translocation of cardiac protein kinase C beta2 in JVS mice. Furthermore, CA + FE prevented the progressive left ventricular dysfunction and dramatically improved the survival rate in JVS mice (survival rate at 400 days after birth: 89 vs. 0%, P < 0.0001). CONCLUSIONS: PPARalpha activation, in addition to l-carnitine supplementation, may rescue the detrimental lipotoxic cardiomyopathy in SCD by improving cardiac energy and lipid metabolism as well as systemic lipid metabolism.
No takes yet. Share an insight, caveat, or question.
ASAI et al. (2006) studied Systemic carnitine deficiency / lipotoxic cardiomyopathy. L-carnitine + fenofibrate vs. Normal chow, fenofibrate alone, or L-carnitine alone was evaluated on Survival rate at 400 days after birth (p=< 0.0001). Combined therapy with L-carnitine and fenofibrate dramatically improved the survival rate at 400 days after birth in JVS mice compared to controls.
Synapse has enriched 10 related papers. Consider them for comparative context: