Zonation of acetate labeling across the liver: implications for studies of lipogenesis by MIDA
Zonation of acetate labeling across the liver: implications for studies of lipogenesis by MIDA
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DOI：
10.1152/ajpendo.1999.277.6.e1022
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发表时间：
1999-12-01
影响因子：
5.1
通讯作者：
Brunengraber, H
中科院分区：
文献类型：
--
作者：
Puchowicz, MA;Bederman, IR;Brunengraber, H
通过[C-13]乙酸酯标记的脂肪酸或胆固醇的质量同位素分布分析（MIDA）测量脂肪生成分数，假设所有肝细胞中脂肪生成乙酰辅酶A不断富集。如果肝脏吸收和释放乙酸盐导致乙酰辅酶A富集的跨肝梯度，则情况并非如此。预先配备经鞘管导管的清醒犬输注葡萄糖和[1，2-C-13（2）]醋酸盐。在动脉（17 μ M，36%）、门静脉（61 μ M，5.4%）和肝静脉（17 μ M，1.0%）中测量乙酸盐的稳定浓度和富集，并计算进入肝脏的混合血（53 μ M，7.4%）。我们还测量了肠道和肝脏中丙酸盐和丁酸盐的平衡。所有肠道释放的丙酸盐和丁酸盐都被肝脏吸收。肝脏中乙酸盐浓度的三倍降低和乙酸盐富集的七倍降低强烈表明脂肪生成乙酰辅酶A的富集在肝脏中降低。因此，MIDA在体内测量的肝脏脂肪生成分数可能被低估。
Measurement of fractional lipogenesis by mass isotopomer distribution analysis (MIDA) of fatty acids or cholesterol labeled from [C-13]acetate assumes constant enrichment of lipogenic acetyl-CoA in all hepatocytes. This would not be the case if uptake and release of acetate by the liver resulted in transhepatic gradients of acetyl-CoA enrichment. Conscious dogs, prefitted with transhepatic catheters, were infused with glucose and [1,2-C-13(2)]acetate. Stable concentrations and enrichments of acetate were measured in artery (17 mu M, 36%), portal vein (61 mu M, 5.4%), and hepatic vein (17 mu M, 1.0%) and were computed for mixed blood entering the liver (53 mu M, 7.4%). We also measured balances of propionate and butyrate across gut and liver. All gut release of propionate and butyrate is taken up, by the liver. The threefold decrease in acetate concentration and the sevenfold decrease in acetate enrichment across the Liver strongly suggest that the enrichment of lipogenic acetyl-CoA decreases across the liver. Thus fractional hepatic lipogenesis measured in vivo by MIDA may be underestimated.