Alterations in adipose tissue and hepatic lipid kinetics in obese men and women with nonalcoholic fatty liver disease
Alterations in adipose tissue and hepatic lipid kinetics in obese men and women with nonalcoholic fatty liver disease
复制标题
DOI：
10.1053/j.gastro.2007.11.038
复制
发表时间：
2008-02-01
期刊：
影响因子：
29.4
通讯作者：
Klein, Samuel
中科院分区：
文献类型：
--
作者：
Fabbrini, Elisa;Mohammed, B. Selma;Klein, Samuel
背景与目的：非酒精性脂肪性肝病（NAFLD）患者的脂肪变性是由于肝内甘油三酯（IHTG）生成与输出之间的失衡所致。本研究旨在评估NAFLD患者脂肪组织和肝脏中的甘油三酯代谢。
方法：采用稳定同位素示踪剂对14名患有NAFLD的非糖尿病肥胖受试者（IHTG，22.7%±2.0%）和14名IHTG含量正常的非糖尿病肥胖受试者（IHTG，3.4%±0.4%）进行脂肪酸、极低密度脂蛋白 - 甘油三酯（VLDL - TG）以及极低密度脂蛋白 - 载脂蛋白B - 100（apoB100）动力学评估，这些受试者在年龄、性别、体重指数和体脂百分比方面相匹配。
结果：与IHTG正常组相比，NAFLD组从脂肪组织向血浆释放棕榈酸的速率更高（分别为85.4±6.6和114.1±8.1 μmol/min，P = 0.01），VLDL - TG分泌速率也更高（分别为11.4±1.1和24.3±3.1 μmol/min，P = 0.001）；两组之间VLDL - apoB100分泌速率无差异。VLDL - TG分泌的增加主要是由于“非系统性”脂肪酸的贡献增加，这些脂肪酸可能来自肝内和腹腔内脂肪的脂解以及从头脂肪生成。在IHTG正常的受试者中，VLDL - TG分泌速率随IHTG含量增加呈线性增加，但当IHTG含量≥10%时达到平台期（r = 0.618，P < 0.001）。
结论：患有NAFLD的肥胖者在脂肪组织（脂解速率增加）和肝脏（VLDL - TG分泌增加）的甘油三酯代谢方面均有显著改变。来自非系统性来源的脂肪酸是VLDL - TG分泌增加的原因。然而，肝脏甘油三酯输出的增加不足以使IHTG含量正常化。
Background & Aims: Steatosis in patients with nonalcoholic fatty liver disease (NAFLD) is due to an imbalance between intrahepatic triglyceride (IHTG) production and export. The purpose of this study was to evaluate TG metabolism in adipose tissue and liver in NAFLD. Methods: Fatty acid, VLDL-TG, and VLDL-apolipoprotein B-100 (apoB100) kinetics were assessed by using stable isotope tracers in 14 nondiabetic obese subjects with NAFLD (IHTG, 22.7% +/- 2.0%) and 14 nondiabetic obese subjects with normal IHTG content (IHTG, 3.4% +/- 0.4%), matched on age, sex, body mass index, and percent body fat. Results: Compared with the normal IHTG group, the NAFLD group had greater rates of palmitate release from adipose tissue into plasma (85.4 +/- 6.6 and 114.1 +/- 8.1 mu mol/min, respectively, P = .01) and VLDL-TG secretion (11.4 +/- 1.1 and 24.3 +/- 3.1 mu mol/min, respectively, P = .001); VLDL-apoB100 secretion rates were not different between groups. The increase in VLDL-TG secretion was primarily due to an increased contribution from "nonsystemic" fatty acids, presumably derived from lipolysis of intrahepatic and intra-abdominal fat and de novo lipogenesis. VLDL-TG secretion rate increased linearly with increasing IHTG content in subjects with normal IHTG but reached a plateau when IHTG content was >= 10% (r = 0.618, P < .001). Conclusions: obese persons with NAFLD have marked alterations in both adipose tissue (increased lipolytic rates) and hepatic (increased VLDL-TG secretion) TG metabolism. Fatty acids derived from nonsystemic sources are responsible for the increase in VLDL-TG secretion. However, the increase in hepatic TG export is not adequate to normalize IHTG content.