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首页> 美国卫生研究院文献>The Journal of Clinical Investigation >Measurement of de novo hepatic lipogenesis in humans using stable isotopes.
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Measurement of de novo hepatic lipogenesis in humans using stable isotopes.

机译：使用稳定同位素测量人的从头肝脏脂肪生成。

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Direct measurement of de novo lipogenesis has not previously been possible in humans. We measured de novo hepatic lipogenesis in normal men by means of stable isotopes and by combining the acetylated-xenobiotic probe technique with mass isotopomer analysis of secreted very low density lipoprotein-fatty acids (VLDL-FA). Sulfamethoxazole (SMX) was administered with [13C]acetate during an overnight fast followed by refeeding with intravenous glucose (7-10 mg/kg of weight per min), oral Ensure (7-10 mg of carbohydrate/kg of weight per min), or a high-carbohydrate mixed-meal breakfast (3.5 g of carbohydrate/kg of weight). Respiratory quotients remained less than 1.0. High-performance liquid chromatography/mass spectrometry-determined enrichments in SMX-acetate attained stable plateau values, and hepatic acetyl-coenzyme A (CoA) dilution rate did not increase with refeeding (approximately 0.024 mmol/kg per min). The fraction of VLDL-palmitate derived from de novo lipogenesis was only 0.91 +/- 0.27% (fasted) and 1.64-1.97% (fed). For stearate, this was 0.37 +/- 0.08% and 0.47-0.64%. Precursor enrichments predicted from isotopomer ratios were close to measured SMX-acetate enrichments, indicating that SMX-acetate samples the true lipogenic acetyl-CoA pool. Stearate synthesis was less than palmitate and the two did not move in parallel. Estimated total VLDL-FA synthesis is less than 500 mg/day. Thus, de novo hepatic lipogenesis is a quantitatively minor pathway, consistent with gas exchange estimates; fatty acid futile cycling (oxidation/resynthesis) is not thermogenically significant; and synthesis rates of different nonessential fatty acids by human liver are not identical in nonoverfed normal men. The contribution and regulation of de novo lipogenesis in other settings can be studied using this technique.
机译：从头脂肪生成的直接测量以前在人类中是不可能的。我们通过稳定的同位素并结合乙酰化的异种生物探针技术与分泌的极低密度脂蛋白脂肪酸（VLDL-FA）的质量同位素异构体分析，测量了正常男性的从头肝脏脂肪生成。在隔夜禁食期间，给予磺胺甲恶唑（SMX）和[13C]乙酸盐，然后以静脉内葡萄糖（7-10 mg / kg体重/分钟）口服补给（7-10 mg碳水化合物/ kg体重/分钟）或高碳水化合物混合餐早餐（每公斤体重3.5克碳水化合物）。呼吸商仍低于1.0。高效液相色谱/质谱法测定的SMX-乙酸盐富集值达到稳定的稳定值，并且肝乙酰辅酶A（CoA）的稀释率不会随进料而增加（约0.024 mmol / kg /分钟）。新生脂肪生成的VLDL-棕榈酸酯的比例仅为0.91 +/- 0.27％（禁食）和1.64-1.97％（进食）。对于硬脂酸盐，这是0.37 +/- 0.08％和0.47-0.64％。由同位素异构体比率预测的前体富集接近于所测得的SMX-乙酸酯富集，表明SMX-乙酸酯采样了真正的脂肪原性乙酰辅酶A库。硬脂酸酯的合成少于棕榈酸酯，并且两者没有平行移动。估计VLDL-FA的总合成量少于500毫克/天。因此，从头肝脂肪生成是一条定量的次要途径，与气体交换估计值相符。脂肪酸无用循环（氧化/再合成）在热学上不重要；非过量正常男性中人非必需脂肪酸的合成和合成速率不同。可以使用这种技术研究在其他情况下新生脂肪形成的贡献和调节。

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