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Metabolism. 2017 Jan;66:14-22. doi: 10.1016/j.metabol.2016.09.005. Epub 2016 Sep 22.

Daily exercise prevents diastolic dysfunction and oxidative stress in a female mouse model of western diet induced obesity by maintaining cardiac heme oxygenase-1 levels.

Author information

1
Division of Cardiovascular Medicine, Diabetes Cardiovascular Center, University of Missouri Columbia, Columbia, MO, USA; Department of Medicine, University of Missouri, Columbia, MO, USA.
2
Department of Medicine, University of Missouri, Columbia, MO, USA; Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA; Division of Endocrinology and Metabolism, Diabetes Cardiovascular Center, University of Missouri, Columbia, MO, USA.
3
Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA.
4
Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA; Department of Radiology, University of Missouri, Columbia, MO, USA.
5
Division of Endocrinology and Metabolism, Diabetes Cardiovascular Center, University of Missouri, Columbia, MO, USA.
6
Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, USA; Biomedical Sciences, University of Missouri, Columbia, MO, USA.
7
Department of Medicine, University of Missouri, Columbia, MO, USA; Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA; Division of Endocrinology and Metabolism, Diabetes Cardiovascular Center, University of Missouri, Columbia, MO, USA; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA. Electronic address: sowersj@health.missouri.edu.

Abstract

OBJECTIVE:

Obesity is a global epidemic with profound cardiovascular disease (CVD) complications. Obese women are particularly vulnerable to CVD, suffering higher rates of CVD compared to non-obese females. Diastolic dysfunction is the earliest manifestation of CVD in obese women but remains poorly understood with no evidence-based therapies. We have shown early diastolic dysfunction in obesity is associated with oxidative stress and myocardial fibrosis. Recent evidence suggests exercise may increase levels of the antioxidant heme oxygenase-1 (HO-1). Accordingly, we hypothesized that diastolic dysfunction in female mice consuming a western diet (WD) could be prevented by daily volitional exercise with reductions in oxidative stress, myocardial fibrosis and maintenance of myocardial HO-1 levels.

MATERIALS/METHODS:

Four-week-old female C57BL/6J mice were fed a high-fat/high-fructose WD for 16weeks (N=8) alongside control diet fed mice (N=8). A separate cohort of WD fed females was allowed a running wheel for the entire study (N=7). Cardiac function was assessed at 20weeks by high-resolution cardiac magnetic resonance imaging (MRI). Functional assessment was followed by immunohistochemistry, transmission electron microscopy (TEM) and Western blotting to identify pathologic mechanisms and assess HO-1 protein levels.

RESULTS:

There was no significant body weight decrease in exercising mice, normalized body weight 14.3g/mm, compared to sedentary mice, normalized body weight 13.6g/mm (p=0.38). Total body fat was also unchanged in exercising, fat mass of 6.6g, compared to sedentary mice, fat mass 7.4g (p=0.55). Exercise prevented diastolic dysfunction with a significant reduction in left ventricular relaxation time to 23.8ms for exercising group compared to 33.0ms in sedentary group (p<0.01). Exercise markedly reduced oxidative stress and myocardial fibrosis with improved mitochondrial architecture. HO-1 protein levels were increased in the hearts of exercising mice compared to sedentary WD fed females.

CONCLUSIONS:

This study provides seminal evidence that exercise can prevent diastolic dysfunction in WD-induced obesity in females even without changes in body weight. Furthermore, the reduction in myocardial oxidative stress and fibrosis and improved HO-1 levels in exercising mice suggests a novel mechanism for the antioxidant effect of exercise.

KEYWORDS:

Diastolic dysfunction; Exercise; Heme oxygenase; Obesity; Oxidative stress

PMID:
27923445
DOI:
10.1016/j.metabol.2016.09.005
[Indexed for MEDLINE]

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