Fermentation Products of Commensal Bacteria Alter Enterocyte Lipid Metabolism
Fermentation Products of Commensal Bacteria Alter Enterocyte Lipid Metabolism
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DOI：
10.1016/j.chom.2020.01.028
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发表时间：
2020-03-11
影响因子：
30.3
通讯作者：
Sansonetti, Philippe J.
中科院分区：
文献类型：
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作者：
Araujo, Joao R.;Tazi, Asmaa;Sansonetti, Philippe J.
尽管公认肠道微生物群具有调节肠道脂质代谢的能力，但特定肠道菌群的作用仍不明确。在这里，我们的目的是了解副干酪乳杆菌和大肠杆菌调节肠细胞脂质代谢的细菌效应和分子机制。结果表明，L.副干酪素抑制肠上皮细胞的乳糜微粒分泌，并通过涉及肠上皮细胞吸收L-乳酸、其转化为丙二酰辅酶A和随后抑制脂质β-氧化的机制促进脂质储存。而E.大肠杆菌还抑制肠细胞的乳糜微粒分泌，但通过涉及肠细胞吸收乙酸盐、其代谢为乙酰辅酶A和AMP以及随后上调AMPK/PGC-1 α/PPAR α途径的机制促进脂质氧化。我们的研究为开发针对肥胖、动脉粥样硬化和营养不良的基于细菌和代谢物的治疗干预开辟了前景，这些干预针对肠上皮细胞中的脂质代谢。
Despite the recognized capacity of the gut microbiota to regulate intestinal lipid metabolism, the role of specific commensal species remains undefined. Here, we aimed to understand the bacterial effectors and molecular mechanisms by which Lactobacillus paracasei and Escherichia coli regulate lipid metabolism in enterocytes. We show that L-lactate produced by L. paracasei inhibits chylomicron secretion from enterocytes and promotes lipid storage by a mechanism involving L-lactate absorption by enterocytes, its conversion to malonyl-CoA, and the subsequent inhibition of lipid beta-oxidation. In contrast, acetate produced by E. coli also inhibits chylomicron secretion by enterocytes but promotes lipid oxidation by a mechanism involving acetate absorption by enterocytes, its metabolism to acetyl-CoA and AMP, and the subsequent upregulation of the AMPK/PGC-1 alpha/PPAR alpha pathway. Our study opens perspectives for developing specific bacteria- and metabolite-based therapeutic interventions against obesity, atherosclerosis, and malnutrition by targeting lipid metabolism in enterocytes.