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

MeSH Terms

Adenosine Triphosphate*
Adenosine*
Animals
Body Weight
Diet
Diet, High-Fat*
DNA, Mitochondrial
Echocardiography
Heart Failure
Microscopy, Electron
Mitochondria
Myocardium
Obesity
Oxidative Phosphorylation
Oxidative Stress
Rats*
Rats, Wistar
Risk Factors
Weights and Measures
Adenosine
Adenosine Triphosphate
DNA, Mitochondrial

Figure

  • Fig. 1 Comparison of the mitral inflow patterns in the diastolic stages between (A) the standard diet and (B) high-fat diet groups.

  • Fig. 2 Histomorphologic images stained with (A, B, ×200) H&E and (C, D, ×3,000; scale bar 1,000 nm) transmission electron microscopic images in the myocardia in the (A, C) standard diet and (B, D) high-fat diet groups.

  • Fig. 3 The mRNA expression levels of a subset of oxidative phosphorylation (OXPHOS) subunits (A), PGC1α (B), antioxidant enzymes (C), Col1A1 (D), and SERCA2 (E) in the myocardia in the standard diet and high-fat diet groups. S, standard diet; H, high-fat diet; NDUFB3, NADH dehydrogenase 1 β subcomplex, 3; NDUFB5, NADH dehydrogenase 1 β subcomplex, 5; NDUFV1, NADH dehydrogenase flavoprotein 1; NDUFS1, NADH dehydrogenase Fe-S protein 1; SDHB, succinate dehydrogenase complex, subunit B; CYC1, cytochrome C1; SURF1, surfeit 1; PGC1α, peroxisome-proliferator-activated receptor γ, co-activator-1α; MnSOD, manganese-containing superoxide dismutase; Prdx1, peroxiredoxin 1; Prdx2, peroxiredoxin 2; Prdx5, peroxiredoxin 5; Col1A1, collagen, type I, α 1; SERCA2, sarcoendoplasmic reticulum calcium transport ATPase 2. aP<0.05; bP<0.01.

  • Fig. 4 Western blot results (A) and relative expression of pAKT (B), NDUFB5 (C), and PGC1α (D) in the myocardia in the standard diet and high-fat diet groups. S, standard diet; H, high-fat diet; pAKT, phospho-Akt; AKT, a serine/threonine kinase, protein kinase B; NDUFB5, NADH dehydrogenase 1-β subcomplex 5; PGC1α, peroxisome-proliferator-activated receptor γ, co-activator-1α; GAPDH, glyceraladehyde-3-phosphate dehydrogenase. aP<0.05.

  • Fig. 5 Mitochondrial DNA copy number (A), optical density of reactive oxygen species damage marker 8-OHdG (B), and ATP levels (C) in the myocardia in the standard diet and high-fat diet groups. S, standard diet; H, high-fat diet; 8-OHdG, 8-hydroxydeoxyguanosine; OD 450 nm, optical density of 8-OHdG as measured at 450 nm; ATP, adenosine triphosphate. aP<0.05.


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Ki-Woon Kang, Ju-Young Ko, Hyunghee Lee, Seung Yong Shin, Wang Soo Lee, Joonhwa Hong, Sang-Wook Kim, Seong-Kyu Lee, Min-Ho Oak
J Korean Med Sci. 2022;37(9):e55.    doi: 10.3346/jkms.2022.37.e55.


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