Is exercise an effective treatment for NASH? Knowns and unknowns

Non-alcoholic steatohepatitis has emerged as one of the most common causes of chronic liver disease in many regions of the world. Exercise and dietary changes constitute cornerstones of overall therapy aimed at achieving weight loss in hopes of ameliorating lipid-induced hepatocellular injury by mobilizing fat out of the liver. Indeed weight loss is known to be effective as evident in several controlled trials and, in the extreme, with bariatric surgery. However, less is known about exercise in the absence of weight loss especially in terms of altering hepatic fat metabolism. As with steatosis, adipose tissue function and other targets of insulin activity, skeletal muscle physiology is closely integrated with overall energy homeostasis and calorie disposal. Although much remains to be learned, increased physical conditioning appears to be closely linked to improved hepatic metabolism independent of changes in body weight. This is of practical importance to patients attempting lifestyle changes who may become unnecessarily discouraged if there is not evidence of associated weight loss as a result of increased activity. Moreover, the degree of physical conditioning represents an unmeasured and potentially confounding variable in most clinical trials of pharmacological intervention in NASH. Clinical investigation is needed to better understand the effects of exercise on liver fat metabolism and on how best to measure the degree of physical conditioning both as a baseline indicator of overall energy homeostasis and an end-point of treatment.