Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart

Saumya Sharma, Julia V. Adrogue, Leonard Golfman, Ivan Uray, John Lemm, Keith A. Youker, George P. Noon, O. H. Frazier, Heinrich Taegtmeyer

Research output: Contribution to journalArticle

505 Scopus citations

Abstract

In animal models of lipotoxicity, accumulation of triglycerides within cardiomyocytes is associated with contractile dysfunction. However, whether intramyocardial lipid deposition is a feature of human heart failure remains to be established. We hypothesized that intramyocardial lipid accumulation is a common feature of non-ischemic heart failure and is associated with changes in gene expression similar to those found in an animal model of lipotoxicity. Intramyocardial lipid staining with oil red O and gene expression analysis was performed on heart tissue from 27 patients (9 female) with non-ischemic heart failure. We determined intramyocardial lipid, gene expression, and contractile function in hearts from 6 Zucker diabetic fatty (ZDF) and 6 Zucker lean (ZL) rats. Intramyocardial lipid overload was present in 30% of non-ischemic failing hearts. The highest levels of lipid staining were observed in patients with diabetes and obesity (BMI > 30). Intramyocardial lipid deposition was associated with an up-regulation of peroxisome proliferator-activated receptor α (PPARα) -regulated genes, myosin heavy chain β (MHC-β), and tumor necrosis factor α (TNF-α). Intramyocardial lipid overload in the hearts of ZDF rats was associated with contractile dysfunction and changes in gene expression similar to changes found in failing human hearts with lipid overload. Our findings identify a subgroup of patients with heart failure and severe metabolic dysregulation characterized by intramyocardial triglyceride overload and changes in gene expression that are associated with contractile dysfunction. - Sharma, S., Adrogue, J. V., Golfman, L., Uray, I., Lemm, J., Youker, K., Noon, G. P., Frazier, O. H., Taegtmeyer, H. Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart.

Original languageEnglish (US)
Pages (from-to)1692-1700
Number of pages9
JournalFASEB Journal
Volume18
Issue number14
DOIs
StatePublished - Nov 2004

Keywords

  • Contractile dysfunction
  • Lipotoxicity
  • Non-ischemic heart failure
  • Triglyceride accumulation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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