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Publication : Early structural and metabolic cardiac remodelling in response to inducible adipose triglyceride lipase ablation.

First Author  Kienesberger PC Year  2013
Journal  Cardiovasc Res Volume  99
Issue  3 Pages  442-51
PubMed ID  23708736 Mgi Jnum  J:218658
Mgi Id  MGI:5618090 Doi  10.1093/cvr/cvt124
Citation  Kienesberger PC, et al. (2013) Early structural and metabolic cardiac remodelling in response to inducible adipose triglyceride lipase ablation. Cardiovasc Res 99(3):442-51
abstractText  AIMS: While chronic alterations in cardiac triacylglycerol (TAG) metabolism and accumulation are associated with cardiomyopathy, it is unclear whether TAG catabolizing enzymes such as adipose triglyceride lipase (ATGL) play a role in acquired cardiomyopathies. Importantly, germline deletion of ATGL leads to marked cardiac steatosis and heart failure in part through reducing peroxisome proliferator-activated receptor alpha (PPARalpha) activity and subsequent fatty acid oxidation (FAO). However, whether ATGL deficiency specifically in adult cardiomyocytes contributes to impaired PPARalpha activity, cardiac function, and metabolism is not known. METHODS AND RESULTS: To study the effects of acquired cardiac ATGL deficiency on cardiac PPARalpha activity, function, and metabolism, we generated adult mice with tamoxifen-inducible cardiomyocyte-specific ATGL deficiency (icAtglKO). Within 4-6 weeks following ATGL ablation, icAtglKO mice had markedly increased myocardial TAG accumulation, fibrotic remodelling, and pathological hypertrophy. Echocardiographic analysis of hearts in vivo revealed that contractile function was moderately reduced in icAtglKO mice. Analysis of energy metabolism in ex vivo perfused working hearts showed diminished FAO rates which was not paralleled by markedly impaired PPARalpha target gene expression. CONCLUSIONS: This study shows that acquired cardiomyocyte-specific ATGL deficiency in adult mice is sufficient to promote fibrotic and hypertrophic cardiomyopathy and impair myocardial FAO in the absence of markedly reduced PPARalpha signalling.
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