A high-fat diet suppresses de novo lipogenesis and desaturation but not elongation and triglyceride synthesis in mice
A high-fat diet suppresses de novo lipogenesis and desaturation but not elongation and triglyceride synthesis in mice
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DOI：
10.1194/jlr.m052308
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发表时间：
2014-12-01
影响因子：
6.5
通讯作者：
Burgess, Shawn C.
中科院分区：
文献类型：
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作者：
Duarte, Joao A. G.;Carvalho, Filipa;Burgess, Shawn C.
细胞内脂质及其合成有助于肥胖相关疾病的机制和并发症。我们描述了一种NMR方法，提供了一个简短的lipidomic分析与并发脂质生物合成通量。氘水给药后，通过氘NMR对特定脂质物质进行位置同位素异构体分析，以检查通过从头脂肪生成（DNL）、FA延长、去饱和和TG-甘油合成的通量。核磁共振法排除了质量同位素法所要求的关于富集地点和可交换氢的某些假设。该方法对DNL的功能、延长、去饱和和甘油酯合成的遗传和药理学增益或损失有响应。在整个喂养期间检查食用高脂肪饮食（HFD）或匹配的低脂饮食35周的BDF 1小鼠，以确定通过这些途径的通量如何促成饮食诱导的脂肪肝和肥胖。HFD小鼠的FA延长和甘油酯合成速率增加。然而，DNL显着抑制，尽管胰岛素抵抗和肥胖。我们的结论是，大多数肝TG在HFD小鼠的肝脏中形成的现有的或摄入的脂质，而不是DNL的再酯化。
Intracellular lipids and their synthesis contribute to the mechanisms and complications of obesity-associated diseases. We describe an NMR approach that provides an abbreviated lipidomic analysis with concurrent lipid biosynthetic fluxes. Following deuterated water administration, positional isotopomer analysis by deuterium NMR of specific lipid species was used to examine flux through de novo lipogenesis (DNL), FA elongation, desaturation, and TG-glycerol synthesis. The NMR method obviated certain assumptions regarding sites of enrichment and exchangeable hydrogens required by mass isotope methods. The approach was responsive to genetic and pharmacological gain or loss of function of DNL, elongation, desaturation, and glyceride synthesis. BDF1 mice consuming a high-fat diet (HFD) or matched low-fat diet for 35 weeks were examined across feeding periods to determine how flux through these pathways contributes to diet induced fatty liver and obesity. HFD mice had increased rates of FA elongation and glyceride synthesis. However DNL was markedly suppressed despite insulin resistance and obesity. We conclude that most hepatic TGs in the liver of HFD mice were formed from the reesterification of existing or ingested lipids, not DNL.