Feasibility of Vigorous-Intensity Interval Training in Adults With Nonalcoholic Steatohepatitis

Background & Significance:

The increasing prevalence of obesity and diabetes has prompted a global epidemic of nonalcoholic fatty liver disease affecting 15-30% of the general population. Of those with nonalcoholic fatty liver disease, 25% develop NASH and are at increased risk for progressive hepatic fibrosis and cirrhosis. NASH-related cirrhosis is now the second leading indication of liver transplantation in the United States. For the treatment of NASH, life-style modification with diet and exercise is mandatory. Diet and exercise-induced weight loss >5% total body weight improves NASH and reverses hepatic fibrosis, the primary determinant of liver related morbidity and mortality. While weight loss has remained fundamental to disease management it is mistaken as the only assessment for exercise-mediated improvements in NASH. Exercise alone has been shown to improve NASH irrespective of weight loss; however, how exercise works is unclear. Defining an understanding of how exercise effectively treats NASH is an urgent and unmet need that will optimize exercise prescriptions and facilitate identifying candidate therapeutic targets that mimic exercise response for those patients unable to sustain life-style modifications.

One potential mechanism for exercise improving NASH is through skeletal muscles' signaling proteins, known collectively as myokines. During exercise, myokines are released from skeletal muscle into the circulation where they communicate with several organs, including the liver. Emerging evidence suggests that myokines - particularly myokine interleukin 6 (IL-6) -directly regulates liver interleukin (IL)-8.

Our preliminary data demonstrates that in NASH patients, serum IL-8 is independently associated with hepatic fibrosis and differentially expressed by fibrotic stage. Whether exercise-mediated myokine IL-6 improves NASH-related fibrosis through reductions in IL-8 remains a gap in knowledge.

Myokine IL-6 release into the circulation has been shown to be dependent on the amount of skeletal muscle involved during exercise and level of exercise intensity. Thus, full-body movements performed at high-intensity may release the greatest amounts of myokine IL-6. Vigorous-intensity interval training (VIIT) has not been tested in patients with NASH. Additionally, VIIT in NAFLD has been traditionally performed on a cycle ergometer or treadmill, which greatly limits maximal skeletal muscle utilization during exercise. Since myokine release from skeletal muscle is hypothesized as a critical mechanism of exercise-mediated benefits in NAFLD, the investigators are proposing conducting a feasibility study of a single VIIT session in patients with NASH using an indoor rower. To measure IL-6 myokine response and subsequent changes in serum IL-8 the investigators will collect blood samples prior, immediately after, and 2-hours following a single VIIT session.