Metabolic adaptations to dietary fat malabsorption in chylomicron-deficient mice
Metabolic adaptations to dietary fat malabsorption in chylomicron-deficient mice
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DOI：
10.1042/0264-6021:3430473
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发表时间：
1999-10-15
影响因子：
4.1
通讯作者：
Hellerstein, MK
中科院分区：
文献类型：
--
作者：
Jung, HR;Turner, SM;Hellerstein, MK
最近开发了乳糜微粒缺乏的小鼠模型，这些小鼠在肝脏中表达人载脂蛋白（apo）B转基因，但在肠中不合成任何apo B。尽管存在严重的肠脂肪吸收不良，但小鼠维持正常浓度的血浆脂质和肝源性含apo B 100的脂蛋白。本文探讨了血脂维持正常的代谢机制，用质量同位素分布分析（MIDA）测定了新生脂肪生成（DNL）和胆固醇生成，并测定了血浆非酯化脂肪酸（NEFA）通量和标记血浆NEFA的肝脏再摄取率。肝脏和血浆三酰甘油（TG）浓度和血浆NEFA通量之间乳糜微粒缺陷小鼠和对照组没有差异。DNL对肝脏TG池的贡献在乳糜微粒缺陷小鼠中仅略高[12 +/- 2.1%（n = 7）与3.7 +/-1.0%（n = 9）;平均值+/-S.E.M.]，而胆固醇生成显著升高。在乳糜微粒缺乏的动物中，血浆NEFA对肝脏TG的贡献率大大升高（62%比23%）。因此，对照组中73%的肝脏TG既不是来自DNL，也不是来自血浆NEFA，这可能反映了乳糜微粒残留的先前贡献，而乳糜微粒缺乏组中只有26%。DNL对脂肪储存的长期贡献达到大致相同的稳态值乳糜微粒缺乏组动物的体脂积累明显低于对照组（约30%）;因此，全身绝对DNL显著降低。我们得出结论，乳糜微粒缺陷小鼠的血浆和肝脏TG库以及含apoB颗粒的肝脏分泌维持在正常水平，不是通过从头脂肪酸合成，而是通过血浆NEFA的更积极的再酯化，取代乳糜微粒的正常主要贡献，并且一些膳食脂肪可以通过apoB非依赖性机制吸收。
A mouse model of chylomicron deficiency was recently developed these mice express a human apolipoprotein (apo) B transgene in the liver but do not synthesize any apoB in the intestine, Despite severe intestinal fat malabsorption, the mice maintain normal concentrations of plasma lipids and liver-derived apoB 100-containing lipoproteins. We investigated the metabolic mechanisms by which plasma lipid levels are kept normal, De novo lipogenesis (DNL) and cholesterogenesis were measured by mass isotopomer distribution analysis (MIDA), plasma non-esterified fatty acid (NEFA) fluxes and hepatic re-esteritication of labelled plasma NEFA were also measured. Hepatic and plasma triacylglycerol (TG) concentrations and plasma NEFA fluxes were not different between chylomicron-deficient mice and controls. The contribution from DNL to the hepatic TG pool was only modestly higher in chylomicron-deficient mice [12 +/- 2.1% (n = 7) compared with 3,7 +/- 1,0% (n = 9); means +/-S.E.M.], whereas cholesterogenesis was markedly elevated. The fractional contribution from plasma NEFA to hepatic TG was greatly elevated in the chylomicron-deficient animals (62% compared with 23%). Accordingly, 73% of hepatic TG was neither from DNL nor from plasma NEFA in controls, presumably reflecting prior contribution from chylomicron remnants, compared with only 26% in the chylomicron-deficient group. The long-term contribution from DNL to adipose fat stores reached approximately the same steady-state values (approximate to 30%) in the two groups, Body fat accumulation was much lower in chylomicron-deficient animals; thus, whole-body absolute DNL was significantly lower, We conclude that plasma and hepatic TG pools and hepatic secretion of apoB-containing particles are maintained at normal levels in chylomicron-deficient mice, not by de novo fatty acid synthesis, but by more avid reesterification of plasma NEFA, replacing the normally predominant contribution from chylomicrons, and that some dietary fat can be absorbed by apoB-independent mechanisms.