Exercise training improves cutaneous microvascular function in nonalcoholic fatty liver disease

Abstract

Pugh CJ, Cuthbertson DJ, Sprung VS, Kemp GJ, Richardson P, Umpleby AM, Green DJ, Cable NT, Jones H. Exercise training improves cutaneous microvascular function in nonalcoholic fatty liver disease. Am J Physiol Endocrinol Metab 305: E50 -E58, 2013. First published May 7, 2013; doi:10.1152/ajpendo.00055.2013.-The leading causes of mortality in nonalcoholic fatty liver disease (NAFLD) relate to cardiovascular disease (CVD). The contribution of nitric oxide (NO) to endothelial function, a surrogate of CVD risk, is currently unknown in NAFLD. We hypothesize that NO-mediated cutaneous microvessel function would be impaired in NAFLD compared with controls and that exercise would enhance microvessel function compared with conventional care. Thirteen NAFLD patients (aged 50 Ϯ 3 yr, BMI 31 Ϯ 1 kg/m 2 ) and seven controls (48 Ϯ 4 yr, 30 Ϯ 2 kg/m 2 ) were studied. NAFLD patients were randomized to either 16 wk of exercise or conventional care. Cutaneous microvessel function was examined using laser Doppler flowmetry combined with intradermal microdialysis of N G -monomethyl-L-arginine to assay the NO dilator response to local forearm heating. Magnetic resonance imaging and spectroscopy quantified abdominal and liver fat, respectively, and cardiorespiratory fitness was assessed. Differences in NO contribution to cutaneous blood flow between NAFLD and control individuals and between interventions were analyzed using general linear modeling. NO contribution to cutaneous blood flow was similar between NAFLD and controls (P ϭ 0.47). Cardiorespiratory fitness was greater following exercise training compared with conventional care. NO contribution to cutaneous blood flow in response to heating at 42°C was 20.4% CVC max (95% CI ϭ 4.4, 36.4) greater following exercise training compared with conventional care (P ϭ 0.02). Exercise training improves cutaneous microvascular NO function in NAFLD patients. The benefit of exercise training compared with conventional care strongly supports a role for exercise in the prevention of CVD in NAFLD. nonalcoholic fatty liver disease; nitric oxide; microvascular function; exercise; exercise training; cutaneous microvessel function NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) is characterized by excess triglyceride accumulation in the liver and is associated with increased liver-related morbidity and mortality. Nevertheless, numerous epidemiological studies have revealed that cardiovascular disease (CVD) accounts for a greater number of deaths than that of liver disease in NAFLD patients (1,30,36), and some report CVD to be the leading cause of mortality (15,30). These findings imply that NAFLD patients are at high risk of cardiovascular events. Endothelial dysfunction, characterized by diminished bioavailability of the antiatherogenic molecule nitric oxide (NO), is the earliest detectable manifestation in the development of atherosclerosis and a strong predictor of future CVD risk in both symptomatic and asymptomatic individuals (17). Although previous cross-sectional studies have shown that NAFLD pati...

External validation of the fatty liver index and lipid accumulation product indices, using 1H-magnetic resonance spectroscopy, to identify hepatic steatosis in healthy controls and obese, insulin-resistant individuals

“…We recruited healthy controls and individuals with components of the metabolic syndrome including being overweight/obese (BMI O25 kg/m 2 ), with a waist circumference O80 cm in females and O94 cm in males, and with at least one additional feature of the metabolic syndrome according to International Diabetes Federation criteria (22). Clinical characteristics of the cohorts have been presented previously in detail (23,24). All participants gave written informed consent, and ethical approval was obtained from the respective local ethics committee.…”

Exercise Training as Treatment of Nonalcoholic Fatty Liver Disease

“…Nine randomized control trials and four uncontrolled studies have investigated the effects of aerobic training in NAFLD (Table 1) [9][10][11][19][20][21][22][23][24][25][26][27][28]. All of the studies included at least one aerobic training experimental group, with three studies containing multiple aerobic training groups of differing exercise intensities [11,22,24].…”

“…All of the studies included at least one aerobic training experimental group, with three studies containing multiple aerobic training groups of differing exercise intensities [11,22,24]. Maximum heart rate (MHR), heart rate reserve (HRR), maximal predicted heart rate (MPHR), metabolic equivalent of task (MET), or VO 2max were used to determine exercise intensity prescriptions-where intensities range from light to moderate (30-39% of HRR, 57-63% of HRR, 2.0-3.9 METs, and 37-45% of VO 2max ) moderate (40-59% of HRR, 64-76% of HRR, 4.0-5.9 METs, and 46-63% of VO 2max ), and vigorous (60-89% of HRR, 77-95% of HRR, 6.0-8.4 METs, and 64-90% of VO 2max ) [9][10][11][19][20][21][22]24,26,27,29]. Exercise modalities included recreational walking, treadmill running, cycle ergometry, cross-training, rowing, and rhythmic exercise [10,11,[20][21][22][23][24][25][26][27].…”

The benefits of exercise for patients with non-alcoholic fatty liver disease

“…With respect to aerobic exercise, these guidelines promote moderate-intensity cardiorespiratory exercise training for ‡30 min on at least 5 days per week, or vigorous cardiorespiratory exercise training for ‡20 min on 3 days per week, or a combination of both and align with global recommendations for health, fitness and disease prevention [10]. Exercise interventions meeting these guidelines consistently demonstrate reduction in liver fat of 10-43% in patients with NAFLD [5,6,[11][12][13][14][15][16].…”

“…Given that cardiovascular disease is the primary cause of mortality in patients with NAFLD, the benefits of exercise extend beyond steatosis. There is substantial evidence for exercise benefiting the secondary vascular and metabolic co-morbidities associated with NAFLD, including insulin resistance, dyslipidemia, inflammation, hypertension [9] and endothelial dysfunction [16,26], which reduces the risk of liverrelated and cardiovascular morbidity and mortality. Indeed, a one Metabolic Equivalent improvement in cardiorespiratory fitness (3.5 ml/kg/min) is associated with a 13 and 15% reduction in all-cause mortality and risk of cardiovascular events, respectively [27].…”