Fabbrini Elisa, deHaseth Dinky, Deivanayagam Sheela, Mohammed B Selma, Vitola Bernadette E, Klein Samuel
Center for Human Nutrition, Washington University School of Medicine, St Louis, Missouri, USA.
Obesity (Silver Spring). 2009 Jan;17(1):25-9. doi: 10.1038/oby.2008.494. Epub 2008 Oct 23.
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.
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.
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).
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.
有假说认为，脂肪酸供应过多会导致脂肪变性以及与非酒精性脂肪性肝病（NAFLD）相关的代谢异常。本研究的目的是评估NAFLD肥胖青少年的脂肪组织脂解活性和脂肪酸释放到血浆中的速率是否增加。
在基础状态（餐后状态）和生理性高胰岛素血症（餐后状态）期间，对肝内甘油三酯（IHTG）含量正常（n = 9；BMI = 37±2 kg/m²；IHTG≤肝脏体积的5.5%）和增加（n = 9；BMI = 36±2 kg/m²；IHTG≥肝脏体积的10%）的肥胖青少年测定棕榈酸动力学。两组在体重、BMI、体脂百分比、年龄、性别和坦纳分期方面相匹配。采用高胰岛素-正常血糖钳夹技术结合氘代棕榈酸示踪剂输注来测定游离脂肪酸（FFA）动力学，并采用磁共振波谱法测定IHTG含量。
在基础状态下，NAFLD患者血浆中全身棕榈酸释放速率高于IHTG含量正常的患者，（87±7 vs. 127±13 μmol/min；P < 0.01），在生理性高胰岛素血症期间也是如此，（24±2 vs. 44±8 μmol/min；P < 0.01）。
这些结果表明，NAFLD肥胖青少年的脂肪组织脂解活性增加，导致全天脂肪酸释放到血浆中的速率增加。这种持续的脂肪酸通量过剩支持了脂肪组织胰岛素抵抗参与脂肪变性发病机制并导致与NAFLD相关的代谢并发症的假说。
