Lipotoxic heart disease in obese rats

Implications for human obesity

Yan Ting Zhou, Paul Grayburn, Asad Karim, Michio Shimabukuro, Moritake Higa, Dany Baetens, Lelio Orci, Roger H Unger

Research output: Contribution to journalArticle

953 Citations (Scopus)

Abstract

To determine the mechanism of the cardiac dilatation and reduced contractility of obese Zucker Diabetic Fatty rats, myocardial triacylglycerol (TG) was assayed chemically and morphologically. TG was high because of underexpression of fatty acid oxidative enzymes and their transcription factor, peroxisome proliferator-activated receptor-α. Levels of ceramide, a mediator of apoptosis, were 2-3 times those of controls and inducible nitric oxide synthase levels were 4 times greater than normal. Myocardial DNA laddering, an index of apoptosis, reached 20 times the normal level. Troglitazone therapy lowered myocardial TG and ceramide and completely prevented DNA laddering and loss of cardiac function. In this paper, we conclude that cardiac dysfunction in obesity is caused by lipoapoptosis and is prevented by reducing cardiac lipids.

Original languageEnglish (US)
Pages (from-to)1784-1789
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number4
DOIs
StatePublished - Feb 15 2000

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Heart Diseases
Triglycerides
Obesity
Ceramides
troglitazone
Apoptosis
Peroxisome Proliferator-Activated Receptors
DNA
Nitric Oxide Synthase Type II
Dilatation
Transcription Factors
Fatty Acids
Lipids
Enzymes
Therapeutics

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Lipotoxic heart disease in obese rats : Implications for human obesity. / Zhou, Yan Ting; Grayburn, Paul; Karim, Asad; Shimabukuro, Michio; Higa, Moritake; Baetens, Dany; Orci, Lelio; Unger, Roger H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 4, 15.02.2000, p. 1784-1789.

Research output: Contribution to journalArticle

Zhou, Yan Ting ; Grayburn, Paul ; Karim, Asad ; Shimabukuro, Michio ; Higa, Moritake ; Baetens, Dany ; Orci, Lelio ; Unger, Roger H. / Lipotoxic heart disease in obese rats : Implications for human obesity. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 4. pp. 1784-1789.
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