Dione Niokhor, Lacroix Sébastien, Taschler Ulrike, Deschênes Thomas, Abolghasemi Armita, Leblanc Nadine, Di Marzo Vincenzo, Silvestri Cristoforo
Département de Médecine, Université Laval, Québec, QC G1V 0A6, Canada.
Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in metabolic Health, Québec, QC G1V 4G5, Canada.
Cells. 2020 Dec 17;9(12):2705. doi: 10.3390/cells9122705.
Monoglyceride lipase (MGLL) regulates metabolism by catabolizing monoacylglycerols (MAGs), including the endocannabinoid 2-arachidonoyl glycerol (2-AG) and some of its bioactive congeners, to the corresponding free fatty acids. knockout mice () exhibit elevated tissue levels of MAGs in association with resistance to the metabolic and cardiovascular perturbations induced by a high fat diet (HFD). The gut microbiome and its metabolic function are disrupted in obesity in a manner modulated by 2-arachidonoyl glycerol (2-AG's) main receptors, the cannabinoid CB1 receptors. We therefore hypothesized that mice have an altered microbiome, that responds differently to diet-induced obesity from that of wild-type (WT) mice. We subjected mice to HFD and assessed changes in the microbiomes after 8 and 22 weeks. As expected, mice showed decreased adiposity, improved insulin sensitivity, and altered circulating incretin/adipokine levels in response to HFD. mice on a chow diet exhibited significantly higher levels of , , and than WT mice. The relative abundance of the and and of the , , _, and genera was significantly altered by HFD in WT but not mice. Differently abundant families were also associated with changes in circulating adipokine and incretin levels in HFD-fed mice. Some gut microbiota family alterations could be reproduced by supplementing 2-AG or MAGs in culturomics experiments carried out with WT mouse fecal samples. We suggest that the altered microbiome of mice contributes to their obesity resistant phenotype, and results in part from increased levels of 2-AG and MAGs.
单甘油酯脂肪酶（MGLL）通过将单酰甘油（MAGs），包括内源性大麻素2-花生四烯酸甘油酯（2-AG）及其一些生物活性类似物，分解为相应的游离脂肪酸来调节新陈代谢。MGLL基因敲除小鼠（MGLL -/-）体内MAGs的组织水平升高，同时对高脂饮食（HFD）引起的代谢和心血管紊乱具有抗性。肠道微生物群及其代谢功能在肥胖状态下会以一种由2-花生四烯酸甘油酯（2-AG）的主要受体——大麻素CB1受体调节的方式受到破坏。因此，我们推测MGLL -/-小鼠的微生物群发生了改变，对饮食诱导的肥胖的反应与野生型（WT）小鼠不同。我们让MGLL -/-小鼠接受高脂饮食，并在8周和22周后评估微生物群的变化。正如预期的那样，MGLL -/-小鼠在高脂饮食后脂肪量减少、胰岛素敏感性提高，循环中肠促胰岛素/脂肪因子水平发生改变。食用普通饮食的MGLL -/-小鼠的[具体物质名称未给出]、[具体物质名称未给出]和[具体物质名称未给出]水平显著高于野生型小鼠。高脂饮食使野生型小鼠中[具体菌属名称未给出]和[具体菌属名称未给出]以及[具体菌属名称未给出]、[具体菌属名称未给出]、[具体菌属名称未给出]和[具体菌属名称未给出]菌属的相对丰度发生显著改变，但MGLL -/-小鼠未出现这种情况。不同丰度的菌科也与高脂饮食喂养小鼠循环中脂肪因子和肠促胰岛素水平的变化有关。在用野生型小鼠粪便样本进行的培养组学实验中，补充2-AG或MAGs可以重现一些肠道微生物群菌科的改变。我们认为，MGLL -/-小鼠微生物群的改变促成了它们的抗肥胖表型，部分原因是2-AG和MAGs水平的升高。
