Endocrinol Metab.  2015 Dec;30(4):557-568. 10.3803/EnM.2015.30.4.557.

Diastolic Dysfunction Induced by a High-Fat Diet Is Associated with Mitochondrial Abnormality and Adenosine Triphosphate Levels in Rats

Affiliations
  • 1Department of Internal Medicine, Eulji University Hospital, Eulji University School of Medicine, Daejeon, Korea. lskendo@hanmail.net
  • 2Department of Dental Hygiene, Eulji University College of Health Science, Seongnam, Korea.
  • 3Department of Biochemistry-Molecular Biology, Eulji University School of Medicine, Daejeon, Korea.

Abstract

BACKGROUND
Obesity is well-known as a risk factor for heart failure, including diastolic dysfunction. However, this mechanism in high-fat diet (HFD)-induced obese rats remain controversial. The purpose
of this study was to investigate whether cardiac dysfunction develops when rats are fed with a HFD for 10 weeks; additionally, we sought to investigate the association between mitochondrial abnormalities, adenosine triphosphate (ATP) levels and cardiac dysfunction.
METHODS
We examined myocardia in Wistar rats after 10 weeks of HFD (45 kcal% fat, n=6) or standard diet (SD, n=6). Echocardiography, histomorphologic analysis, and electron microscopy were performed. The expression levels of mitochondrial oxidative phosphorylation (OXPHOS) subunit genes, peroxisome-proliferator-activated receptor gamma co-activator-1alpha (PGC1alpha) and anti-oxidant enzymes were assessed. Markers of oxidative stress damage, mitochondrial DNA copy number and myocardial ATP level were also examined.
RESULTS
After 10 weeks, the body weight of the HFD group (349.6+/-22.7 g) was significantly higher than that of the SD group (286.8+/-14.9 g), and the perigonadal and epicardial fat weights of the HFD group were significantly higher than that of the SD group. Histomorphologic and electron microscopic images were similar between the two groups. However, in the myocardium of the HFD group, the expression levels of OXPHOS subunit NDUFB5 in complex I and PGC1alpha, and the mitochondrial DNA copy number were decreased and the oxidative stress damage marker 8-hydroxydeoxyguanosine was increased, accompanied by reduced ATP levels.
CONCLUSION
Diastolic dysfunction was accompanied by the mitochondrial abnormality and reduced ATP levels in the myocardium of 10 weeks-HFD-induced rats.

Keyword

Obesity; Diastolic dysfunction; Mitochondria
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