{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:56:59Z","timestamp":1787590619177,"version":"build-2736575974"},"reference-count":34,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fonds de la Recherche Scientifique (FNRS FRFS-WELBIO)","award":["FNRS T.0030.21"],"award-info":[{"award-number":["FNRS T.0030.21"]}]},{"name":"Fonds de la Recherche Scientifique (FNRS FRFS-WELBIO)","award":["2022-3916"],"award-info":[{"award-number":["2022-3916"]}]},{"DOI":"10.13039\/501100002661","name":"Projet de Recherche PDR-convention","doi-asserted-by":"publisher","award":["FNRS T.0030.21"],"award-info":[{"award-number":["FNRS T.0030.21"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002661","name":"Projet de Recherche PDR-convention","doi-asserted-by":"publisher","award":["2022-3916"],"award-info":[{"award-number":["2022-3916"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"name":"La Caixa (NeuroGut)","award":["FNRS T.0030.21"],"award-info":[{"award-number":["FNRS T.0030.21"]}]},{"name":"La Caixa (NeuroGut)","award":["2022-3916"],"award-info":[{"award-number":["2022-3916"]}]},{"DOI":"10.13039\/501100003745","name":"WoM Lundgren grant","doi-asserted-by":"publisher","award":["FNRS T.0030.21"],"award-info":[{"award-number":["FNRS T.0030.21"]}],"id":[{"id":"10.13039\/501100003745","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003745","name":"WoM Lundgren grant","doi-asserted-by":"publisher","award":["2022-3916"],"award-info":[{"award-number":["2022-3916"]}],"id":[{"id":"10.13039\/501100003745","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Obesity is associated with a cluster of metabolic disorders, chronic low-grade inflammation, altered gut microbiota, increased intestinal permeability, and alterations of the lipid mediators of the expanded endocannabinoid (eCB) signaling system, or endocannabinoidome (eCBome). In the present study, we characterized the profile of the eCBome and related oxylipins in the small and large intestines of genetically obese (ob\/ob) and diabetic (db\/db) mice to decipher possible correlations between these mediators and intestinal inflammation and gut microbiota composition. Basal lipid and gene expression profiles, measured by LC\/MS-MS-based targeted lipidomics and qPCR transcriptomics, respectively, highlighted a differentially altered intestinal eCBome and oxylipin tone, possibly linked to increased mRNA levels of inflammatory markers in db\/db mice. In particular, the duodenal levels of several 2-monoacylglycerols and N-acylethanolamines were increased and decreased, respectively, in db\/db mice, which displayed more pronounced intestinal inflammation. To a little extent, these differences were explained by changes in the expression of the corresponding metabolic enzymes. Correlation analyses suggested possible interactions between eCBome\/oxylipin mediators, cytokines, and bacterial components and bacterial taxa closely related to intestinal inflammation. Collectively, this study reveals that db\/db mice present a higher inflammatory state in the intestine as compared to ob\/ob mice, and that this difference is associated with profound and potentially adaptive or maladaptive, and partly intestinal segment-specific alterations in eCBome and oxylipin signaling. This study opens the way to future investigations on the biological role of several poorly investigated eCBome mediators and oxylipins in the context of obesity and diabetes-induced gut dysbiosis and inflammation.<\/jats:p>","DOI":"10.3390\/cells12030411","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T01:57:07Z","timestamp":1674698227000},"page":"411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A Lipidomics- and Transcriptomics-Based Analysis of the Intestine of Genetically Obese (ob\/ob) and Diabetic (db\/db) Mice: Links with Inflammation and Gut Microbiota"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1343-5500","authenticated-orcid":false,"given":"Francesco","family":"Suriano","sequence":"first","affiliation":[{"name":"Metabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), UCLouvain, Universit\u00e9 Catholique de Louvain, Av. E. Mounier, 73 B1.73.11, 1200 Brussels, Belgium"},{"name":"Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), WELBIO Department, WEL Research Institute, Avenue Pasteur, 6, 1300 Wavre, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4081-9550","authenticated-orcid":false,"given":"Claudia","family":"Manca","sequence":"additional","affiliation":[{"name":"Quebec Heart and Lung Institute Research Centre, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"},{"name":"Institute of Nutrition and Functional Foods, Centre NUTRISS, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5944-7200","authenticated-orcid":false,"given":"Nicolas","family":"Flamand","sequence":"additional","affiliation":[{"name":"Quebec Heart and Lung Institute Research Centre, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5503-107X","authenticated-orcid":false,"given":"Matthias","family":"Van Hul","sequence":"additional","affiliation":[{"name":"Metabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), UCLouvain, Universit\u00e9 Catholique de Louvain, Av. E. Mounier, 73 B1.73.11, 1200 Brussels, Belgium"},{"name":"Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), WELBIO Department, WEL Research Institute, Avenue Pasteur, 6, 1300 Wavre, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2115-6082","authenticated-orcid":false,"given":"Nathalie M.","family":"Delzenne","sequence":"additional","affiliation":[{"name":"Metabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), UCLouvain, Universit\u00e9 Catholique de Louvain, Av. E. Mounier, 73 B1.73.11, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5635-1545","authenticated-orcid":false,"given":"Cristoforo","family":"Silvestri","sequence":"additional","affiliation":[{"name":"Quebec Heart and Lung Institute Research Centre, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"},{"name":"Institute of Nutrition and Functional Foods, Centre NUTRISS, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2040-2448","authenticated-orcid":false,"given":"Patrice D.","family":"Cani","sequence":"additional","affiliation":[{"name":"Metabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), UCLouvain, Universit\u00e9 Catholique de Louvain, Av. E. Mounier, 73 B1.73.11, 1200 Brussels, Belgium"},{"name":"Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), WELBIO Department, WEL Research Institute, Avenue Pasteur, 6, 1300 Wavre, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1490-3070","authenticated-orcid":false,"given":"Vincenzo","family":"Di Marzo","sequence":"additional","affiliation":[{"name":"Quebec Heart and Lung Institute Research Centre, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"},{"name":"Institute of Nutrition and Functional Foods, Centre NUTRISS, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"},{"name":"Joint International Research Unit for Chemical and Biomolecular Research on the Microbiome and Its Impact on Metabolic Health and Nutrition (JIRU-MicroMeNu) between Universit\u00e9 Laval and the Italian Consiglio Nazionale delle Ricerche, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, 80078 Pozzuoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"ref_1","unstructured":"GBD 2019 Risk Factors Collaborators (2020). Global burden of 87 risk factors in 204 countries and territories, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet, 396, 1223\u20131249."},{"key":"ref_2","unstructured":"Mahmood, T., Arulkumaran, S., and Chervenak, F. (2020). Obesity and Obstetrics, Elsevier. [2nd ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1136\/gutjnl-2021-326789","article-title":"Gut microbiome and health: Mechanistic insights","volume":"71","author":"Tilg","year":"2022","journal-title":"Gut"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/nm.4185","article-title":"Signals from the gut microbiota to distant organs in physiology and disease","volume":"22","author":"Schroeder","year":"2016","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1053\/j.gastro.2008.10.080","article-title":"Microbes in Gastrointestinal Health and Disease","volume":"136","author":"Neish","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1042\/BCJ20160510","article-title":"Introduction to the human gut microbiota","volume":"474","author":"Thursby","year":"2017","journal-title":"Biochem. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.2337\/db06-1491","article-title":"Metabolic endotoxemia initiates obesity and insulin resistance","volume":"56","author":"Cani","year":"2007","journal-title":"Diabetes"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.2337\/db07-1403","article-title":"Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet-Induced Obesity and Diabetes in Mice","volume":"57","author":"Cani","year":"2008","journal-title":"Diabetes"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"953196","DOI":"10.3389\/fimmu.2022.953196","article-title":"Diet, microbiota, and the mucus layer: The guardians of our health","volume":"13","author":"Suriano","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41582-019-0284-z","article-title":"Cannabinoids and the expanded endocannabinoid system in neurological disorders","volume":"16","author":"Cristino","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Di Marzo, V., and Wang, J. (2015). The Endocannabinoidome: The World of Endocannabinoids and Related Mediators, Academic Press Books-Elsevier.","DOI":"10.1016\/B978-0-12-420126-2.00018-3"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/msb.2010.46","article-title":"The endocannabinoid system links gut microbiota to adipogenesis","volume":"6","author":"Muccioli","year":"2010","journal-title":"Mol. Syst. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.1096\/fj.201601346R","article-title":"The role of CB1 in intestinal permeability and inflammation","volume":"31","author":"Karwad","year":"2017","journal-title":"FASEB J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s00418-018-1719-0","article-title":"Cellular localization and regulation of receptors and enzymes of the endocannabinoid system in intestinal and systemic inflammation","volume":"151","author":"Grill","year":"2019","journal-title":"Histochem. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6495","DOI":"10.1038\/ncomms7495","article-title":"Adipose tissue NAPE-PLD controls fat mass development by altering the browning process and gut microbiota","volume":"6","author":"Geurts","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/s41467-018-08051-7","article-title":"Intestinal epithelial N-acylphosphatidylethanolamine phospholipase D links dietary fat to metabolic adaptations in obesity and steatosis","volume":"10","author":"Everard","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.bbi.2017.09.001","article-title":"Antibiotic-induced microbiota perturbation causes gut endocannabinoidome changes, hippocampal neuroglial reorganization and depression in mice","volume":"67","author":"Guida","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1194\/jlr.RA119000424","article-title":"Germ-free mice exhibit profound gut microbiota-dependent alterations of intestinal endocannabinoidome signaling","volume":"61","author":"Manca","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s40168-021-01097-8","article-title":"Novel insights into the genetically obese (ob\/ob) and diabetic (db\/db) mice: Two sides of the same coin","volume":"9","author":"Suriano","year":"2021","journal-title":"Microbiome"},{"key":"ref_20","first-page":"159056","article-title":"Exploring the endocannabinoidome in genetically obese (ob\/ob) and diabetic (db\/db) mice: Links with inflammation and gut microbiota","volume":"1867","author":"Suriano","year":"2022","journal-title":"Biochim. Biophys. Acta (BBA) -Mol. Cell Biol. Lipids"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1139\/y59-099","article-title":"A rapid method of total lipid extraction and purification","volume":"37","author":"Bligh","year":"1959","journal-title":"Can. J. Biochem. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.cell.2006.07.035","article-title":"The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells","volume":"126","author":"Ivanov","year":"2006","journal-title":"Cell"},{"key":"ref_23","first-page":"47","article-title":"Endocannabinoids and the gastrointestinal tract","volume":"29","author":"Massa","year":"2006","journal-title":"J. Endocrinol. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/labinvest.2015.129","article-title":"Regulation of intestinal SGLT1 by catestatin in hyperleptinemic type 2 diabetic mice","volume":"96","author":"Rieg","year":"2016","journal-title":"Lab. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Archambault, A.-S., Tinto, F., Dumais, \u00c9., Rakotoarivelo, V., Kostrzewa, M., Plante, P.-L., Martin, C., Simard, M., Silvestri, C., and Pouliot, R. (2021). Biosynthesis of the Novel Endogenous 15-Lipoxygenase Metabolites N-13-Hydroxy-octodecadienoyl-ethanolamine and 13-Hydroxy-octodecadienoyl-glycerol by Human Neutrophils and Eosinophils. Cells, 10.","DOI":"10.3390\/cells10092322"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1111\/bph.13580","article-title":"The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations","volume":"174","author":"Petrosino","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1124\/mol.117.110841","article-title":"N-Acyl Amino Acids (Elmiric Acids): Endogenous Signaling Molecules with Therapeutic Potential","volume":"93","author":"Burstein","year":"2018","journal-title":"Mol. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13106","DOI":"10.1523\/JNEUROSCI.2919-09.2009","article-title":"T-Type Calcium Channel Inhibition Underlies the Analgesic Effects of the Endogenous Lipoamino Acids","volume":"29","author":"Barbara","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"136377","DOI":"10.1016\/j.neulet.2021.136377","article-title":"Mini-review: Dissecting receptor-mediated stimulation of TRPV4 in nociceptive and inflammatory pathways","volume":"770","author":"Peng","year":"2022","journal-title":"Neurosci. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/bs.apha.2017.03.002","article-title":"Role of Nonneuronal TRPV4 Signaling in Inflammatory Processes","volume":"79","author":"Rajasekhar","year":"2017","journal-title":"Adv. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1152\/physiolgenomics.00114.2017","article-title":"Gut microbiome may contribute to insulin resistance and systemic inflammation in obese rodents: A meta-analysis","volume":"50","author":"Jiao","year":"2018","journal-title":"Physiol. Genom."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Terzo, S., Mul\u00e8, F., Caldara, G.F., Baldassano, S., Puleio, R., Vitale, M., Cassata, G., Ferrantelli, V., and Amato, A. (2020). Pistachio Consumption Alleviates Inflammation and Improves Gut Microbiota Composition in Mice Fed a High-Fat Diet. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010365"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11420","DOI":"10.1039\/D1FO01422F","article-title":"Dihydroquercetin supplement alleviates colonic inflammation potentially through improved gut microbiota community in mice","volume":"12","author":"Wan","year":"2021","journal-title":"Food Funct."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"784211","DOI":"10.3389\/fmicb.2021.784211","article-title":"Caffeic Acid Supplement Alleviates Colonic Inflammation and Oxidative Stress Potentially Through Improved Gut Microbiota Community in Mice","volume":"12","author":"Wan","year":"2021","journal-title":"Front. Microbiol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/3\/411\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:15:38Z","timestamp":1760120138000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/3\/411"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,25]]},"references-count":34,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["cells12030411"],"URL":"https:\/\/doi.org\/10.3390\/cells12030411","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,25]]}}}