Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease
Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease
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DOI：
10.1172/jci23621
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发表时间：
2005-05-01
影响因子：
15.9
通讯作者：
Parks, EJ
中科院分区：
文献类型：
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作者：
Donnelly, KL;Smith, CI;Parks, EJ
非酒精性脂肪性肝病（NAFLD）的特征是肝脏三酰甘油（TAG）过度蓄积、炎症以及肝脏损伤。本研究的目的是直接量化NAFLD中肝脏和血浆脂蛋白TAG的生物学来源。安排进行医学指征肝活检的患者（5名男性和4名女性；年龄44±10岁）接受稳定同位素静脉输注和口服4天，以标记和追踪血清非酯化脂肪酸（NEFAs）、膳食脂肪酸以及从头脂肪生成（DNL）途径产生的脂肪酸，这些脂肪酸存在于肝脏组织和脂蛋白TAG中。通过气相色谱/质谱法分析肝脏和脂蛋白TAG脂肪酸。NAFLD患者肥胖，伴有空腹高甘油三酯血症和高胰岛素血症。在肝脏中所占的TAG中，59.0%±9.9%的TAG来自NEFAs；26.1%±6.7%来自DNL；14.9%±7.0%来自膳食。极低密度脂蛋白（VLDL）中的标记模式与肝脏相似，并且在整个4天的标记过程中，肝脏显示出对脂肪和膳食脂肪酸的交替利用。DNL在空腹状态下升高，且无昼夜变化。这些定量代谢数据证明，外周脂肪酸升高和DNL都促成了NAFLD中肝脏和脂蛋白脂肪的蓄积。
Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of excess liver triacylglycerol (TAG), inflammation, and liver damage. The goal of the present study was to directly quantify the biological sources of hepatic and plasma lipoprotein TAG in NAFLD. Patients (5 male and 4 female; 44 10 years of age) scheduled for a medically indicated liver biopsy were infused with and orally fed stable isotopes for 4 days to label and track serum nonesterified fatty acids (NEFAs), dietary fatty acids, and those derived from the de novo lipogenesis (DNL) pathway, present in liver tissue and lipoprotein TAG. Hepatic and lipoprotein TAG fatty acids were analyzed by gas chromatography/mass spectrometry. NAFLD patients were obese, with fasting hypertriglyceridemia and hyperinsulinemia. Of the TAG accounted for in liver, 59.0% +/- 9.9% of TAG arose from NEFAs; 26.1% +/- 6.7%, from DNL; and 14.9% +/- 7.0%, from the diet. The pattern of labeling in VLDL was similar to that in liver, and throughout the 4 days of labeling, the liver demonstrated reciprocal use of adipose and dietary fatty acids. DNL was elevated in the fasting state and demonstrated no diurnal variation. These quantitative metabolic data document that both elevated peripheral fatty acids and DNL contribute to the accumulation of hepatic and lipoprotein fat in NAFLD.