Effect of obesity reduction on preservation of heart function and attenuation of left ventricular remodeling, oxidative stress and inflammation in obese mice.
BACKGROUND
Obesity 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.


RESULTS
Eight-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).


CONCLUSIONS
Impaired LVEF, enhanced LV remodeling, inflammation, fibrosis, oxidative stress and apoptosis were reversed by reduction in mouse obesity.
Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Hui-Ting
HT
Wang
Chu-Feng
CF
Liu
Tzu-Hsien
TH
Tsai
Yung-Lung
YL
Chen
Hsueh-Wen
HW
Chang
Ching-Yen
CY
Tsai
Steve
S
Leu
Yen-Yi
YY
Zhen
Han-Tan
HT
Chai
Sheng-Ying
SY
Chung
Sarah
S
Chua
Chia-Hung
CH
Yen
Hon-Kan
HK
Yip
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D005355:Fibrosis; D006334:Heart Function Tests; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000150:complications* / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008954:Models, Biological; D009206:Myocardium / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D018384:Oxidative Stress / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014463:Ultrasonography; D014661:Vasoconstriction; D020257:Ventricular Remodeling / Q000502:physiology*; D015431:Weight Loss
D015415:Biomarkers; D012333:RNA, Messenger; D017382:Reactive Oxygen Species