Alterations in fatty acid kinetics in obese adolescents with increased intrahepatic triglyceride content

Abstract

Objective: It has been hypothesized that excessive fatty acid availability contributes to steatosis and the metabolic abnormalities associated with nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to evaluate whether adipose tissue lipolytic activity and the rate of fatty acid release into plasma are increased in obese adolescents with NAFLD.

Methods: Palmitate kinetics were determined in obese adolescents with normal (n = 9; BMI = 37 +/- 2 kg/m(2); intrahepatic triglyceride (IHTG) <or=5.5% of liver volume) and increased (n = 9; BMI = 36 +/- 2 kg/m(2); IHTG >or= 10% of liver volume) IHTG content during the basal state (postabsorptive condition) and during physiological hyperinsulinemia (postprandial condition). Both groups were matched on body weight, BMI, percent body fat, age, sex, and Tanner stage. The hyperinsulinemic-euglycemic clamp procedure, in conjunction with a deuterated palmitate tracer infusion, was used to determine free-fatty acid (FFA) kinetics, and magnetic resonance spectroscopy was used to determine IHTG content.

Results: The rate of whole-body palmitate release into plasma was greater in subjects with NAFLD than those with normal IHTG content during basal conditions, (87 +/- 7 vs. 127 +/- 13 micromol/min; P < 0.01) and during physiological hyperinsulinemia, (24 +/- 2 vs. 44 +/- 8 micromol/min; P < 0.01).

Discussion: These results demonstrate that adipose tissue lipolytic activity is increased in obese adolescents with NAFLD and results in an increase in the rate of fatty acid release into plasma throughout the day. This continual excess in fatty acid flux supports the hypothesis that adipose insulin resistance is involved in the pathogenesis of steatosis and contributes to the metabolic complications associated with NAFLD.

Figure 1

Whole-body palmitate kinetics during basal conditions and insulin infusion in subjects with normal and increased (nonalcoholic fatty liver disease (NAFLD)) intrahepatic triglyceride (IHTG) content. The data are expressed as (a) total palmitate rate of appearance (Ra) into plasma, (b) palmitate Ra per kg fat mass (FM), which represents adipose tissue lipolytic activity in relationship to endogenous fat stores, and (c) palmitate rate of disappearance (Rd) from plasma per kg fat-free mass (FFM), which represents FFA availability to oxidative tissues.*Value significantly different from corresponding value in the normal IHTG group, P ≤ 0.01. ^†Value significantly different from corresponding basal value, P < 0.001.