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March 1, 2006Cardiovascular Research

Combined therapy with PPARα agonist and l-carnitine rescues lipotoxic cardiomyopathy due to systemic carnitine deficiency

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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 (89% vs. 0%, P < 0.0001).

Why the study?

Does combined therapy with fenofibrate and L-carnitine improve survival and cardiac metabolism in a murine model of systemic carnitine deficiency?

Population

Wild-type and juvenile visceral steatosis mice; 4 to 8 animals per group for experiments and 9 to 11 animals…

Comparison

0.1% L-carnitine + 0.2% fenofibrate containing… vs Normal chow, 0.2% fenofibrate containing chow…

Design

Preclinical

Follow-up

up to 400 days after birth

Authors

TAT ASAIKOKenji OkumuraRTR TAKAHASHI

Discussion

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Member takes

Overview

Findings remain preclinical; leaves open translation of combined L-carnitine and fenofibrate to human carnitine deficiency.

Structured PICO

Does combined therapy with fenofibrate and L-carnitine improve survival and cardiac metabolism in a murine model of systemic carnitine deficiency?

P
Population
Wild-type and JVS mice (a murine model of systemic carnitine deficiency) fed normal chow or chow containing fenofibrate, L-carnitine, or both from 4 weeks of age.
I
Intervention
0.1% L-carnitine + 0.2% fenofibrate containing chow from 4 weeks of age
C
Comparator
Normal chow, 0.2% fenofibrate containing chow alone, or 0.1% L-carnitine containing chow alone
O
Outcome
Ventricular hypertrophy, plasma and myocardial triglyceride levels, myocardial ATP content, myocardial 1,2-diacylglycerol (DAG) composition, and survival ratesurrogate

Main Result

Absolute Event Rate: 89% vs 0%

p-value: p=< 0.0001

Combined PPARalpha activation and L-carnitine supplementation rescues lipotoxic cardiomyopathy and improves survival in a murine model of systemic carnitine deficiency.

Cite This Study

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 (89% vs. 0%, P < 0.0001).

synapsesocial.com/papers/6a6f503fac440176ef280261https://doi.org/10.1016/j.cardiores.2006.02.005
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Dietary fish oil attenuates cardiac hypertrophy in lipotoxic cardiomyopathy due to systemic carnitine deficiency2005 · 36 citations
  2. 2The cardiac phenotype induced by PPARα overexpression mimics that caused by diabetes mellitus2002 · 879 citations
  3. 3Expression of protein kinase C beta in the heart causes hypertrophy in adult mice and sudden death in neonates.1997 · 230 citations
  4. 4Cytoplasmic Signaling Pathways That Regulate Cardiac Hypertrophy2001 · 690 citations
  5. 5Phenotypic manifestations of the OCTN2 V295X mutation: Sudden infant death and carnitine‐responsive cardiomyopathy in Roma families2004 · 38 citations