Exercise Dose and Nonalcoholic Fatty Liver Disease (ED)

The purpose of this research is to provide a better understanding of how exercise (walking) affects non-alcoholic fatty liver disease (NAFLD) in overweight people. NAFLD, which is common in obese people, occurs when the liver has too much fat.

Non-alcoholic fatty liver disease (NAFLD) affects about 33% of adults in the United States. The prevalence of NAFLD is four to five times higher in obese than lean persons and is associated with insulin resistance and the metabolic syndrome. Decreasing calorie intake and increasing physical activity has been recommended as primary therapy for NAFLD, but the independent effect of aerobic exercise is unknown. The current exercise guidelines for disease prevention and weight management range from 150 min/wk, recommended by the Centers for Disease Control and the American College of Sports Medicine, to 300 min/wk, recommended by the Institute of Medicine. However, it is not known whether aerobic exercise alone can improve NAFLD, and which recommended dose of exercise might have the most beneficial effects. The purpose of this proposal is to determine the effect of moderate intensity endurance exercise on: 1) hepatic fat content; 2) hepatic lipoprotein kinetics; and 3) plasma inflammatory markers. We hypothesize that aerobic exercise will decrease hepatic fat content, improve VLDL kinetics, and decrease inflammation in a dose-dependent fashion. The results from this study will help determine exercise guidelines for obese patients with NAFLD, and lay the groundwork for future studies evaluating the effects of exercise on metabolic diseases associated with obesity. This proposal involves conducting a randomized controlled trial that will randomize obese subjects with NAFLD (> 10% hepatic fat content) to one of two groups: Group 1 (Control, no exercise) and Group 2 (Moderate Intensity Aerobic Exercise- 150 min/wk to 300 min/wk of supervised exercise performed at 45-55% of O2 max).

Subjects will serve as controls, continuing current diet and activity levels. Subjects will get monthly weights by the investigator at the research center.

Insulin action in liver (suppression of glucose production), muscle (stimulation of glucose uptake), and adipose tissue (suppression of lipolysis).

Inclusion Criteria: Age 18-65 with Nonalcoholic Fatty Liver Disease as determined by MRS Exclusion Criteria: Medical History Diabetes Heart Disease Asthma/Lung disease Injury that prevents exercise Social history Drinking More than one drink per day Binge drinking on the weekends (more than 3 or 4 drinks per weekend day) Smoking It's OK if they were a previous smoker, but they need to have quit more than 6 months ago Exercise They must exercise less than one hour per week Medications: must be on stable regimen of ANY medication for at least 3 months Beta-Blockers Lipid/cholesterol lowering medications: Oral hypoglycemics (anti-diabetes medications - some like metformin are indicated for pre-diabetes) Hormone replacement therapy If the woman is pre-menopausal, it is OK if she is on birth control as long as she has been on it over 3 months Weight history Weight <300 lbs BMI 30 to 45 Weight stable - <10lbs weight loss or gain in the last 3 months

Sullivan S, Kirk EP, Mittendorfer B, Patterson BW, Klein S. Randomized trial of exercise effect on intrahepatic triglyceride content and lipid kinetics in nonalcoholic fatty liver disease. Hepatology. 2012 Jun;55(6):1738-45. doi: 10.1002/hep.25548. Epub 2012 Apr 25.