Acetate and butyrate are the major substrates for de novo lipogenesis in rat colonic epithelial cells.
Acetate and butyrate are the major substrates for de novo lipogenesis in rat colonic epithelial cells.
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DOI：
10.1093/jn/133.11.3509
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发表时间：
2003-11
期刊：
影响因子：
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通讯作者：
K. Zambell;M. Fitch;S. Fleming
中科院分区：
文献类型：
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作者：
K. Zambell;M. Fitch;S. Fleming
这些实验的目的是研究用于脂质合成的底物的来源和结肠上皮细胞将底物掺入脂质的途径。在重复中，将细胞暴露于该实验中评价的所有处理。通过比较几种14 C标记底物进入脂质的相对掺入率，在本研究中使用的体外条件下，乙酸盐对脂质的碳贡献显著大于丙酸盐、丁酸盐、葡萄糖或谷氨酰胺。其他主要的碳贡献者是丁酸和3-羟基丁酸。葡萄糖、谷氨酰胺和丙酸盐的贡献很小。（-）-羟基柠檬酸盐不影响乙酸或丁酸碳掺入脂质，即使它抑制结肠ATP-柠檬酸裂解酶。这些数据表明，用于结肠细胞合成脂质的SCFA碳不太可能作为柠檬酸盐转运到胞质溶胶。竞争实验表明，酮体和丁酸有助于脂肪生成的单一前体库。然而，酮体并没有显著抑制醋酸盐掺入脂质。3 H2O和14 C-乙酸酯的掺入磷脂比游离脂肪酸和甘油三酯显着更大，这表明脂肪生成的主要作用是膜合成。总之，结肠细胞合成脂质的途径与肝脏不同，主要是将SCFA和酮体掺入脂质中，并在一定程度上使用柠檬酸盐（如果有的话）将乙酰基单位从线粒体转运到胞质溶胶中。
The objective of these experiments was to investigate the source of substrates used for lipid synthesis and the pathways of substrate incorporation into lipids by epithelial cells of the colon. Within replicates, cells were exposed to all treatments evaluated in that experiment. By comparing the relative incorporation rates of several 14C-labeled substrates into lipids, acetate made a significantly larger carbon contribution to lipids than propionate, butyrate, glucose or glutamine under the in vitro conditions utilized in this study. Other major carbon contributors were butyrate and 3-hydroxybutyrate. Glucose, glutamine and propionate made only minor contributions. (-)-Hydroxycitrate did not affect the incorporation of acetate or butyrate carbon into lipids, even though it inhibited colonic ATP-citrate lyase. These data suggest that SCFA carbon used in the synthesis of lipids by colonocytes is not likely transported to the cytosol as citrate. Competition experiments suggest that ketone bodies and butyrate contribute to a single precursor pool for lipogenesis. Ketone bodies did not significantly suppress acetate incorporation into lipid, however. Incorporation of 3H2O and 14C-acetate was significantly greater into phospholipids than into free fatty acids and triacylglycerides, suggesting that the major role of lipogenesis is for membrane synthesis. In conclusion, colonocytes appear to synthesize lipids using a pathway distinct from the liver by incorporating mainly SCFA and ketone bodies into lipids, and by using citrate to a limited extent, if at all, to transport acetyl units from the mitochondria to the cytosol.