Obesogenic high fat western diet induces oxidative stress and apoptosis in rat heart

Mol Cell Biochem. 2010 Nov;344(1-2):221-30. doi: 10.1007/s11010-010-0546-y. Epub 2010 Jul 31.

Abstract

Feeding Wistar rats a high calorie "Western" diet (45% fat) for up to 48 weeks induces obesity and cardiac dysfunction, while a high fat diet (60% fat) induces obesity only. Here we investigated the molecular "footprints" of the two forms of diet-induced obesity in the heart. In rats fed Western diet for a long term, cardiac mRNA transcript levels of malic enzyme were decreased (-72%, P < 0.05), suggesting impaired anaplerotic flux of the Krebs cycle (KC) and mitochondrial dysfunction. In addition, there was a marked decrease in the expression of the transcription factor MEF2C (myocyte enhancer factor 2C) and its target gene SERCA2a (sarco-endo-plasmic reticulum Ca(2+)-ATPase). Oxidative stress was reflected in reduced transcript levels of manganese superoxide dismutase, glutathione peroxidase 1, and increased protein levels of mitochondrial transcription factor A, suggesting compensatory mitochondrial biogenesis in the face of increased mitochondrial damage. Oxidant injury was accompanied by increased protein glycosylation, increased transcript levels of glutamine fructose 6-phosphate amidotransferase 2, and decreased protein levels of acetyl Co-A carboxylase. Lastly, apoptosis was evident by TUNEL positivity and elevated mRNA transcript levels and activity of caspase 3. Consistent with these results, protein levels of Bcl2 were markedly reduced. We conclude that inadequate supplementation of KC intermediates due to reduced levels of malic enzyme, downregulation of MEF2C and its target gene SERCA2a, oxidative stress, and programmed cell death are all potential contributors to contractile dysfunction of the heart.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis*
  • Dietary Fats / administration & dosage*
  • Glycosylation
  • In Situ Nick-End Labeling
  • MEF2 Transcription Factors
  • Myocardium / metabolism*
  • Myogenic Regulatory Factors / genetics
  • Oxidative Stress*
  • PPAR alpha / genetics
  • Rats
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics

Substances

  • Dietary Fats
  • MEF2 Transcription Factors
  • MEF2C protein, rat
  • Myogenic Regulatory Factors
  • PPAR alpha
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases