Exercise training reverses endothelial dysfunction in nonalcoholic fatty liver disease
Pugh, Christopher J. A.
Sprung, Victoria S.
Kemp, Graham J.
Umpleby, A. Margot
Green, Daniel J.
Cable, N. Timothy
Cuthbertson, Daniel J.
American Physiological Society
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Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular disease (CVD). Endothelial dysfunction is an early manifestation of atherosclerosis and an important prognostic marker for future cardiovascular events. The aim of this study was twofold: to examine 1) the association between liver fat, visceral adipose tissue (VAT), and endothelial dysfunction in obese NAFLD patients and 2) the impact of supervised exercise training on this vascular defect. Brachial artery endothelial function was assessed by flow-mediated dilatation (FMD) in 34 obese NAFLD patients and 20 obese controls of similar age and cardiorespiratory fitness [peak oxygen uptake (V˙ O2 peak)] (48 ! 2 vs. 47 ! 2 yr; 27 ! 1 vs. 26 ! 2 ml·kg"1·min"1"1). Magnetic resonance imaging and spectroscopy quantified abdominal and liver fat, respectively. Twenty-one NAFLD patients completed either 16 wk of supervised moderate-intensity exercise training (n # 13) or conventional care (n # 8). Differences between NAFLD and controls were compared using independent t-tests and effects of interventions by analysis of covariance. NAFLD patients had higher liver fat [11.6% (95% CI # 7.4, 18.1), P $ 0.0005] and VAT [1.6 liters (95% CI # 1.2, 2.0), P $ 0.0001] than controls and exhibited impaired FMD compared with controls ["3.6% (95% CI # "4.9, "2.2), P $ 0.0001]. FMD was inversely correlated with VAT (r # "0.54, P # 0.001) in NAFLD, although the impairment in FMD remained following covariate adjustment for VAT [3.1% (95% CI # 1.8, 4.5), P $ 0.001]. Exercise training, but not conventional care, significantly improved V˙ O2 peak [9.1 ml·kg"1·min"1 (95% CI # 4.1, 14.1); P #0.001] and FMD [3.6% (95% CI # 1.6, 5.7), P # 0.002]. Endothelial dysfunction in NAFLD cannot be fully explained by excess VAT but can be reversed with exercise training; this has potential implications for the primary prevention of CVD in NAFLD.
American Journal of Physiology; Heart and Circulatory Physiology
Pugh C.J., Sprung V.S., Kemp G.J., Richardson P., Shojaee-Moradie F., Umpleby A.M., Green D.J., Cable N.T., Jones H. and Cuthbertson D.J. (2014) 'Exercise training reverses endothelial dysfunction in nonalcoholic fatty liver disease', American Journal of Physiology; Heart & Circulatory Physiology, 307(9), H1298-1306
This article was published in American Journal of Physiology; Heart and Circulatory Physiology on 01 November 2014, available at http://dx.doi.org/10.1152/ajpheart.00306.2014
We would like to thank the European Foundation for the Study of Diabetes for funding this study [09/H1008/1]
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