Abstract
BackgroundObesity is an important cardiovascular risk factor. This study tested the effect of obesity reduction on preserving left ventricular ejection fraction (LVEF) and attenuating inflammation, oxidative stress and LV remodeling in obese mice.Methods and resultsEight-week-old C57BL/6 J mice (n=24) were equally divided into control (fed a control diet for 22 weeks), obesity (high-fat diet, 22 weeks), and obese reduction (OR) (high-fat diet, 14 weeks; then control diet, 8 weeks). Animals were sacrificed at post 22-week high-fat diet and the LV myocardium collected. Heart weight, body weight, abdominal-fat weight, total cholesterol level and fasting blood glucose were higher in obesity than in control and OR (all p<0.001). Inflammation measured by mRNA expressions of IL-6, MMP-9, PAI-1 and leptin and protein expression of NF-κB was higher, whereas anti-inflammation measured by mRNA expressions of adiponectin and INF-γ was lower in obesity than in control and OR (all p<0.003). Oxidative protein expressions of NOX-1, NOX-2 and oxidized protein were higher, whereas expression of anti-oxidant markers HO-1 and NQO-1 were lower (all p<0.01); and apoptosis measured by Bax and caspase 3 was higher, whereas anti-apoptotic Bcl-2 was lower in obesity as compared with control and OR (all p<0.001). The expressions of fibrotic markers phosphorylated Smad3 and TGF-β were higher, whereas expression of anti-fibrotic phosphorylated Smad1/5 and BMP-2 were lower (all p<0.02); and LVEF was lower, whereas the LV remodeling was higher in obesity than in control and OR (all p<0.001).ConclusionImpaired LVEF, enhanced LV remodeling, inflammation, fibrosis, oxidative stress and apoptosis were reversed by reduction in mouse obesity.
Highlights
Obesity is a major global problem that affects health and quality of life [1,2,3]
Impaired left ventricular ejection fraction (LVEF), enhanced LV remodeling, inflammation, fibrosis, oxidative stress and apoptosis were reversed by reduction in mouse obesity
Using a high fat diet-induced mouse model of obesity, the aim of this study was to test the hypotheses that, in obese mice: 1) inflammation, oxidative stress, fibrosis and apoptosis were significantly enhanced in the LV myocardium; and 2) LV function was significantly impaired, whereas LV remodeling was remarkably increased in obese mice; and 3) molecular-cellular perturbations, LV dysfunction and LV remodeling were significantly reversed after reduction in obesity
Summary
Obesity is a major global problem that affects health and quality of life [1,2,3]. Age-related increases in obesity are associated with a notably higher prevalence of metabolic disease, several common cancers, and numerous other cardiovascular diseases [4,5,6]. Abundant data suggest that oxidative stress and inflammatory signaling are interrelated, but that their upregulation can lead to inhibition in insulin response to glucose and contribute to atherosclerosis, cardiovascular diseases and their associated features [5,13,14,15,16,17,18,19]. The study [20] has further identified that enhancement of these biomarkers played an essential role on deteriorating the heart function. Whether these biomarkers are up-regulated in setting of obesity remains uncertain. This study tested the effect of obesity reduction on preserving left ventricular ejection fraction (LVEF) and attenuating inflammation, oxidative stress and LV remodeling in obese mice
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