Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, INSERM U1202, 75015 Paris, France.
Unité de Lymphopoïèse, Institut Pasteur, INSERM U1223, 75015 Paris, France.
Cell Host Microbe. 2020 Mar 11;27(3):358-375.e7. doi: 10.1016/j.chom.2020.01.028. Epub 2020 Feb 25.
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-1α/PPARα 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.
尽管肠道微生物群被认为能够调节肠道脂质代谢，但特定共生物种的作用仍未确定。在这里，我们旨在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物和分子机制。我们表明，副干酪乳杆菌产生的 L-乳酸通过肠细胞吸收 L-乳酸、将其转化为丙二酰辅酶 A，以及随后抑制脂质β氧化的机制，抑制肠细胞乳糜微粒的分泌并促进脂质储存。相比之下，大肠杆菌产生的乙酸也通过肠细胞吸收乙酸、将其代谢为乙酰辅酶 A 和 AMP，以及随后上调 AMPK/PGC-1α/PPARα 途径的机制，抑制肠细胞乳糜微粒的分泌，但促进脂质氧化。我们的研究为开发针对肠细胞脂质代谢的特定基于细菌和代谢物的治疗干预措施，以对抗肥胖、动脉粥样硬化和营养不良开辟了新的前景。
