Fatty Acid Metabolism in the Liver, Measured by Positron Emission Tomography, Is Increased in Obese Individuals
Fatty Acid Metabolism in the Liver, Measured by Positron Emission Tomography, Is Increased in Obese Individuals
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DOI：
10.1053/j.gastro.2010.05.039
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发表时间：
2010-09-01
期刊：
影响因子：
29.4
通讯作者：
Nuutila, Pirjo
中科院分区：
文献类型：
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作者：
Iozzo, Patricia;Bucci, Marco;Nuutila, Pirjo
背景与目的：肝脏脂毒性是肥胖相关疾病的结果，也是肥胖相关疾病的一部分。研究脂肪酸在肝脏中的代谢是一个挑战。我们将正电子发射断层扫描（PET）的（11）C-棕榈酸成像与房室模型相结合，以确定猪和人类肝脏FA摄取、氧化和储存以及甘油三酯释放的速率。方法：麻醉猪在禁食（n = 3）或血糖正常的高胰岛素血症（n = 3）期间进行（11）C-棕榈酸酯PET成像。在动脉、门静脉和肝静脉血中测定脂肪酸的代谢产物。然后在15名人类受试者（8名肥胖受试者）中测试成像方法;血浆（11）C-棕榈酸动力学分析用于量化全身和内脏脂解。研究结果：在猪中，PET衍生和相应的测量FA通量（FA摄取，酯化和甘油三酯FA释放）没有差异，并相互关联。在人类中，与对照组相比，肥胖受试者的肝脏FA氧化增加（平均值±标准误，0.16 ± 0.01 vs 0.08 ± 0.01 μ mol/min/mL; P = 0.0007）;肥胖受试者和对照组之间的FA摄取和酯化率没有差异。肝脏FA氧化与血浆胰岛素水平（r = 0.61，P = 0.016）、脂肪组织（r = 0.58，P = 0.024）和全身胰岛素抵抗（r = 0.62，P = 0.015）相关。肝脏脂肪酸酯化与全身释放到血浆中的脂肪酸相关（r = 0.71，P = 0.003）。结论：PET成像可用于测量肝脏中的FA代谢。通过使用这项技术，我们发现肥胖个体在脂肪组织胰岛素抵抗的背景下增加了FA的肝脏氧化，并增加了来自内脏脂肪的FA通量。来自内脏脂肪的FA通量与相应贮库的质量成比例。
BACKGROUND & AIMS: Hepatic lipotoxicity results from and contributes to obesity-related disorders. It is a challenge to study human metabolism of fatty acids (FAs) in the liver. We combined (11)C-palmitate imaging by positron emission tomography (PET) with compartmental modeling to determine rates of hepatic FA uptake, oxidation, and storage, as well as triglyceride release in pigs and human beings. METHODS: Anesthetized pigs underwent (11)C-palmitate PET imaging during fasting (n = 3) or euglycemic hyperinsulinemia (n = 3). Metabolic products of FAs were measured in arterial, portal, and hepatic venous blood. The imaging methodology then was tested in 15 human subjects (8 obese subjects); plasma (11)C-palmitate kinetic analyses were used to quantify systemic and visceral lipolysis. RESULTS: In pigs, PET-derived and corresponding measured FA fluxes (FA uptake, esterification, and triglyceride FA release) did not differ and were correlated with each other. In human beings, obese subjects had increased hepatic FA oxidation compared with controls (mean +/- standard error of the mean, 0.16 +/- 0.01 vs 0.08 +/- 0.01 mu mol/min/mL; P = .0007); FA uptake and esterification rates did not differ between obese subjects and controls. Liver FA oxidation correlated with plasma insulin levels (r = 0.61, P = .016), adipose tissue (r = 0.58, P = .024), and systemic insulin resistance (r = 0.62, P = .015). Hepatic FA esterification correlated with the systemic release of FA into plasma (r = 0.71, P = .003). CONCLUSIONS: PET imaging can be used to measure FA metabolism in the liver. By using this technology, we found that obese individuals have increased hepatic oxidation of FA, in the context of adipose tissue insulin resistance, and increased FA flux from visceral fat. FA flux from visceral fat is proportional with the mass of the corresponding depot.