Objective:
Insulin resistance and visceral adiposity are predisposing factors for fatty liver disease. This study was undertaken to evaluate the weight loss effects on liver function (ALT, AST, GGT).
Methods:
90 overweight/obese, mild hypertensive men without medications or liver dysfunction were randomized into the 3 weight loss (WL) regimens over 24 weeks. WL was achieved with i) a mild calorie restricted diet alone (D alone; 1800kcal/day, 55% carbohydrate, 30% protein, 15% fat), ii) mild exercise alone (EX alone; 1-hr walking), or iii) a combination with a mild calorie restricted diet + exercise (D+EX) over 24 weeks. BMI, waist/hip ratio (W/H), total body fat-mass, blood pressure (BP), plasma norepinephrine (NE), fasting insulin, glucose, HOMA-IR, total cholesterol (Tch), triglyceride (TG), and liver function (ALT, AST, GGT) were measured every 4 weeks over 24 weeks with WL.
Results:
At entry period, BMI, fat-mass, W/H, BP levels, plasma NE, HOMA-IR, Tch, TG, ALT, AST, and GGT were similar between the 3 groups. At 24 weeks, the D+EX group had significantly higher prevalence of normalizations of BMI and BP levels (53.3%, 56.7%, respectively) compared to the D alone (13.3%, 23.3%, 30.0%) or EX alone (26.6%, 23.3%). In the D alone group, significant decreases in plasma NE and TG was observed at 2 weeks followed by significant reductions in Tch, body weight, fat mass, and HOMA at 8 weeks. Significant reductions in W/H, BP and GGT were also observed at 8 weeks, and ALT and AST decreased gradually but significantly at 12 weeks. On the other hand, in the EX alone group, significant fat loss and significant reduction in W/H, HOMA-IR and GGT were observed at 4 weeks. Body weight and plasma NE decreased significantly at 8 weeks, and significant BP reduction and decreases in TG and Tch were occurred at 12 weeks followed by decreases in ALT and AST at 16 weeks. Reductions in GGT were similar between the D alone and D+EX groups, but the groups including D had greater reduction in GGT, ALT and AST compared to the EX alone group. In the combination group (D+EX group), every improvement was observed earlier and stronger. Significant suppression on plasma NE and TG was at 2 weeks, decreases in HOMA, Tch, weight, fat-mass, W/H, systolic BP and GGT were at 4 weeks, and diastolic BP, ALT, and AST were at 8 weeks. In all subjects, reductions in HOMA-IR preceded to decreases in liver function parameters (GGT, ALT, and AST), and reductions in GGT was followed by decreases in ALT or AST. In multiple regression analyses, at both period of entry and 24-week, HOMA-IR was a significant determinant for GGT, TG and Tch. At entry and 24-week periods, Tch, but not TG, was a significant determinant for GGT, ALT, and AST.
Conclusions:
Improvement of insulin resistance associated with WL may play an important role of improvement of liver function during lifestyle modifications. WL is an effective treatment for fatty liver disease associated with obesity.
Gut permeability is related to body weight, fatty liver disease, and insulin resistance in obese individuals undergoing weight reduction