PulseTrendingJournal ClubResearchersJournalsExplore
Instagram
HomeTrendingJournal ClubExplore
Synapse
⌘+K
Synapse
January 1, 2002Journal of Clinical InvestigationOpen Access

The cardiac phenotype induced by PPARα overexpression mimics that caused by diabetes mellitus

View Full Paper
Ask AI
Bookmark
Share

Population

Mice with cardiac-restricted overexpression of PPARalpha (MHC-PPAR)

Design

Preclinical

Key result

Cardiac-restricted overexpression of PPARα in mice increased myocardial fatty acid oxidation by 64% and decreased glucose oxidation by 63%, mimicking the metabolic phenotype of diabetic cardiomyopathy.

Authors

BFBrian N. FinckJLJohn J. LehmanTLTeresa C. Leone

Discussion

Loading...

Member takes

Overview

Supports PPARα as mediator of diabetic cardiomyopathy-like metabolism; leaves open clinical relevance in humans.

Key Points

  • To explore how PPARalpha affects cardiac energy metabolism and contributes to diabetic cardiomyopathy.
  • Generated MHC-PPAR mice with cardiac-restricted PPARalpha overexpression.
  • Analyzed gene expression related to fatty acid and glucose metabolism in MHC-PPAR hearts.
  • Measured myocardial fatty acid oxidation rates and glucose uptake.
  • Increased fatty acid oxidation rates in MHC-PPAR mice (exact rates not specified).
  • Decreased glucose uptake and oxidation noted in MHC-PPAR hearts (exact rates not specified).
  • Exhibited signs of diabetic cardiomyopathy such as ventricular hypertrophy and altered systolic function.

Structured PICO

P
Population
Mice with cardiac-restricted overexpression of PPARalpha (MHC-PPAR)
I
Intervention
Cardiac-restricted overexpression of PPARalpha
O
Outcome
Cardiac phenotype including gene expression profiles, myocardial fatty acid and glucose metabolic rates, ventricular hypertrophy, and systolic ventricular dysfunctionsurrogate

Main Result

Absolute Event Rate: 294% vs 179%

p-value: p=<0.05

Cardiac-restricted overexpression of PPARalpha in mice induces metabolic derangements and cardiomyopathy that mimic the diabetic heart, highlighting the maladaptive role of altered energy metabolism in diabetic cardiomyopathy.

Limitations

  • The mechanism involved in the increased myocardial fatty acid uptake remains unknown
  • Cannot exclude the possibility that lipid synthesis pathways are activated directly by PPARα in the MHC-PPAR heart
  • Unlikely that all of the observed gene regulatory effects occur directly via PPARα

Cite This Study

Finck et al. (2002) studied Diabetic cardiomyopathy. Cardiac-restricted overexpression of PPARα vs. Nontransgenic littermates was evaluated on Myocardial palmitate oxidation rate (nmol/min/g dry weight) (p=<0.05). Cardiac-restricted overexpression of PPARα in mice increased myocardial fatty acid oxidation by 64% and decreased glucose oxidation by 63%, mimicking the metabolic phenotype of diabetic cardiomyopathy.

synapsesocial.com/papers/6a116f1087fe85de623633abhttps://doi.org/10.1172/jci14080
View Full Paper
Ask AI
Bookmark
Share