Metabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), UCLouvain, Université catholique de Louvain, Av. E. Mounier, 73 B1.73.11, 1200 Brussels, Belgium.
Quebec Heart and Lung Institute Research Centre, Université Laval, Quebec City, QC G1V 0A6, Canada; Centre NUTRISS, Institute of Nutrition and Functional Foods, Université Laval, Quebec City, QC G1V 0A6, Canada.
Biochim Biophys Acta Mol Cell Biol Lipids. 2022 Jan;1867(1):159056. doi: 10.1016/j.bbalip.2021.159056. Epub 2021 Oct 1.
Obesity and type 2 diabetes are two interrelated metabolic disorders characterized by insulin resistance and a mild chronic inflammatory state. We previously observed that leptin (ob/ob) and leptin receptor (db/db) knockout mice display a distinct inflammatory tone in the liver and adipose tissue. The present study aimed at investigating whether alterations in these tissues of the molecules belonging to the endocannabinoidome (eCBome), an extension of the endocannabinoid (eCB) signaling system, whose functions are important in the context of metabolic disorders and inflammation, could reflect their different inflammatory phenotypes.
The basal eCBome lipid and gene expression profiles, measured by targeted lipidomics and qPCR transcriptomics, respectively, in the liver and subcutaneous or visceral adipose tissues, highlighted a differentially altered eCBome tone, which may explain the impaired hepatic function and more pronounced liver inflammation remarked in the ob/ob mice, as well as the more pronounced inflammatory state observed in the subcutaneous adipose tissue of db/db mice. In particular, the levels of linoleic acid-derived endocannabinoid-like molecules, of one of their 12-lipoxygenase metabolites and of Trpv2 expression, were always altered in tissues exhibiting the highest inflammation. Correlation studies suggested the possible interactions with some gut microbiota bacterial taxa, whose respective absolute abundances were significantly different between ob/ob and the db/db mice.
The present findings emphasize the possibility that bioactive lipids and the respective receptors and enzymes belonging to the eCBome may sustain the tissue-dependent inflammatory state that characterizes obesity and diabetes, possibly in relation with gut microbiome alterations.
肥胖症和 2 型糖尿病是两种相互关联的代谢紊乱疾病，其特征为胰岛素抵抗和轻度慢性炎症状态。我们之前观察到，瘦素（ob/ob）和瘦素受体（db/db）敲除小鼠的肝脏和脂肪组织中表现出明显的炎症特征。本研究旨在研究属于内源性大麻素组（eCBome）的分子在这些组织中的变化情况，内源性大麻素（eCB）信号系统的扩展，其功能在代谢紊乱和炎症背景下非常重要，是否能反映它们不同的炎症表型。
通过靶向脂质组学和 qPCR 转录组学分别测量肝脏和皮下或内脏脂肪组织中的基础内源性大麻素组脂质和基因表达谱，突出了不同的内源性大麻素组变化，这可能解释了 ob/ob 小鼠肝脏功能受损和更明显的肝脏炎症，以及 db/db 小鼠皮下脂肪组织中观察到的更明显的炎症状态。特别是，在表现出最高炎症的组织中，亚油酸衍生的内源性大麻素样分子、它们的 12-脂氧合酶代谢物之一和 TRPV2 表达的水平总是发生改变。相关性研究表明，它们可能与一些肠道微生物群细菌分类群相互作用，ob/ob 和 db/db 小鼠之间这些分类群的绝对丰度存在显著差异。
本研究结果强调了内源性大麻素组中的生物活性脂质及其相应的受体和酶可能维持肥胖症和糖尿病特征的组织依赖性炎症状态，可能与肠道微生物组的改变有关。
