Introduction
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide with a reported current global prevalence of 25.2%.1 While hepatic steatosis without concomitant metabolic disease is associated with a mild increase in the risk of liver morbidity, including fibrosis and cirrhosis, hepatic steatosis significantly increases the risk of cardiovascular disease (CVD) and cancer mortality.2 In adults with hepatic steatosis in the presence of obesity and insulin resistance, the risk of fibrosis is significantly increased.3 High hepatic steatosis levels have also been shown to be mechanistically involved in insulin resistance and contribute to the progression from obesity with normal glycaemic control and insulin sensitivity to insulin resistance and type 2 diabetes (T2DM).4 As the global epidemic of obesity and T2DM are realised, it is, therefore, expected that the prevalence of MASLD will increase.5 The future burden of MASLD is expected to be considerable, and there is a great need to establish effective treatments for MASLD, particularly for adults with comorbid obesity and insulin resistance.
Lifestyle intervention, involving regular exercise (training) is well known to have a wide range of health benefits including improving cardiorespiratory fitness, muscular function and reducing risk of CVD and some cancers.6 Exercise training enhances insulin sensitivity and glycaemic control in those with normal glycaemia and overweight/obesity.7 In people with pre-diabetes, exercise training significantly reduces risk of progression to T2DM in addition to improving fitness and reducing CVD risk factors.8 In those with T2DM, regular exercise improves glycaemic control, fitness, CVD risk and a range of diabetes-related complications.9 Consequently, despite some differences between specific exercise guidance, the consensus from major international authorities is that adults with overweight/obesity and/or pre-diabetes/T2DM should engage in regular bouts of aerobic and resistance type exercise.10 11
There are limited pharmacological interventions that are effective and safe for reducing hepatic steatosis.12 Despite generally small studies and sample sizes, collectively the available evidence demonstrates that exercise training alone (in the absence of dietary modification) can improve hepatic steatosis in adults with obesity,13 those with prediabetes14 and those with T2DM.15 Furthermore, exercise can reduce hepatic steatosis without meaningful reduction in body weight,16 this is important because, although weight loss consequent to lifestyle intervention is known to significantly reduce hepatic steatosis,17 meaningful weight loss is difficult for most people to achieve and sustain.10 Yet, despite the emphasis on combined aerobic and resistance exercise in current guidelines,10 all studies to date have used exclusively aerobic or resistance training interventions to examine the therapeutic effect of exercise training on hepatic steatosis, and the vast majority of these have involved exclusive aerobic exercise interventions in small experimental samples. These data have demonstrated that aerobic exercise involving either moderate-intensity continuous training (MICT) and/or HIIT may be beneficial for reducing hepatic steatosis. Furthermore, low-volume HIIT may reduce hepatic steatosis15 and may yield similar improvements in cardiorespiratory fitness and glycaemia while being more time effective than traditional HIIT.18 Low-volume HIIT may be more a more achievable method of exercise for some people who experience a lack of time as a barrier to engaging in exercise.19 The combination of low-volume HIIT and resistance training may improve hepatic steatosis, glycaemia and body composition. However, the effect of resistance training on hepatic steatosis remains unclear in a small number of trials, which may be related to the length of the intervention and participants insulin sensitivity.20 21 The effect of combined low-volume high-intensity aerobic exercise with progressive resistance training (PRT) on hepatic steatosis is not known.
Given its possible efficacy for reducing hepatic steatosis, and the established multiplicity of its health benefits, the primary aim of this study was to examine the utility of combined high-intensity aerobic exercise and resistance training on hepatic steatosis in adults with overweight/obesity. Secondary aims were to examine the effects of the intervention on cardiometabolic health, to conduct a sensitivity analysis of weight stable participants and to examine subgroups of participants based on glucose status. To investigate this, a randomised controlled trial was employed, involving regular low-volume HIIT and resistance training and serial measurement of hepatic steatosis and cardiometabolic outcomes in a large sample of previously inactive adults with obesity and either normal glucose (NG), pre-diabetes or newly diagnosed T2DM.