{"doi":"10.3390/ijms231810549","title":"Diet-Induced Gut Barrier Dysfunction Is Exacerbated in Mice Lacking Cannabinoid 1 Receptors in the Intestinal Epithelium","abstract":"<jats:p>The gut barrier provides protection from pathogens and its function is compromised in diet-induced obesity (DIO). The endocannabinoid system in the gut is dysregulated in DIO and participates in gut barrier function; however, whether its activity is protective or detrimental for gut barrier integrity is unclear. We used mice conditionally deficient in cannabinoid receptor subtype-1 (CB1R) in the intestinal epithelium (intCB1−/−) to test the hypothesis that CB1Rs in intestinal epithelial cells provide protection from diet-induced gut barrier dysfunction. Control and intCB1−/− mice were placed for eight weeks on a high-fat/sucrose Western-style diet (WD) or a low-fat/no-sucrose diet. Endocannabinoid levels and activity of their metabolic enzymes were measured in the large-intestinal epithelium (LI). Paracellular permeability was tested in vivo, and expression of genes for gut barrier components and inflammatory markers were analyzed. Mice fed WD had (i) reduced levels of endocannabinoids in the LI due to lower activity of their biosynthetic enzymes, and (ii) increased permeability that was exacerbated in intCB1−/− mice. Moreover, intCB1−/− mice fed WD had decreased expression of genes for tight junction proteins and increased expression of inflammatory markers in LI. These results suggest that CB1Rs in the intestinal epithelium serve a protective role in gut barrier function in DIO.</jats:p>","journal":"International Journal of Molecular Sciences","year":2022,"id":643624,"datarank":0.42498200160843247,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.0,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":492409,"name":"Nicholas V. DiPatrizio","orcid":"0000-0001-8423-0695","position":1,"is_corresponding":false},{"id":773688,"name":"Mark B. Wiley","orcid":"0000-0002-3039-9361","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Diet-Induced Gut Barrier Dysfunction Is Exacerbated in Mice Lacking Cannabinoid 1 Receptors in the Intestinal Epithelium","abstract":"<jats:p>The gut barrier provides protection from pathogens and its function is compromised in diet-induced obesity (DIO). The endocannabinoid system in the gut is dysregulated in DIO and participates in gut barrier function; however, whether its activity is protective or detrimental for gut barrier integrity is unclear. We used mice conditionally deficient in cannabinoid receptor subtype-1 (CB1R) in the intestinal epithelium (intCB1−/−) to test the hypothesis that CB1Rs in intestinal epithelial cells provide protection from diet-induced gut barrier dysfunction. Control and intCB1−/− mice were placed for eight weeks on a high-fat/sucrose Western-style diet (WD) or a low-fat/no-sucrose diet. Endocannabinoid levels and activity of their metabolic enzymes were measured in the large-intestinal epithelium (LI). Paracellular permeability was tested in vivo, and expression of genes for gut barrier components and inflammatory markers were analyzed. Mice fed WD had (i) reduced levels of endocannabinoids in the LI due to lower activity of their biosynthetic enzymes, and (ii) increased permeability that was exacerbated in intCB1−/− mice. Moreover, intCB1−/− mice fed WD had decreased expression of genes for tight junction proteins and increased expression of inflammatory markers in LI. These results suggest that CB1Rs in the intestinal epithelium serve a protective role in gut barrier function in DIO.</jats:p>","is_dataset_classified":null,"base_score":2.833213344056216,"endowment":2.833213344056216,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36142461","pmcid":"PMC9504303","openalex_id":"https://openalex.org/W4296794455","authors":[],"funders":[{"funder_name":"National Institute of Diabetes and Digestive Kidney Diseases","grant_id":"R01DK119498","title":null},{"funder_name":"National Institute of Diabetes and Digestive Kidney Diseases","grant_id":"874959","title":null},{"funder_name":"Center for Medicinal Cannabis Research","grant_id":"Pilot Project 874959","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01DK119498-02","title":"Gut-brain endocannabinoid signaling in feeding behavior and obesity"}],"total_grants":4,"fwci":2.4449,"citation_percentile":0.88207226,"influential_citations":0,"citation_trend":[{"year":2023,"count":5},{"year":2024,"count":5},{"year":2025,"count":5},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/23/18/10549/pdf?version=1663052049","host_type":"journal"},{"url":"https://www.mdpi.com/1422-0067/23/18/10549/pdf?version=1663052049","host_type":"publisher"},{"url":"https://www.mdpi.com/1422-0067/23/18/10549/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/ijms231810549","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36142461","host_type":"repository"},{"url":"https://doaj.org/article/7ed91c27c8c747d683675920340c5a30","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/ijms231810549","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9504303","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9504303","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9504303?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.3390/ijms231810549","host_type":""}],"fields_of_study":["Cannabis and Cannabinoid Research","Dietary Effects on Health","Biochemical Analysis and Sensing Techniques","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","Diet, High-Fat","Endocannabinoids","Intestinal Mucosa","Mice","Mice, Inbred C57BL","Obesity","Receptor, Cannabinoid, CB1","Receptors, Cannabinoid","Tight Junction Proteins"],"mesh_terms":["Animals","Intestinal Mucosa","Mice, Inbred C57BL","Obesity","Receptors, Cannabinoid","Receptor, Cannabinoid, CB1","Mice","Diet, High-Fat","Tight Junction Proteins","Endocannabinoids"],"keywords":["Barrier function","Endocannabinoid system","Intestinal epithelium","Paracellular transport","Intestinal permeability","Tight junction","Biology","Anandamide","Endocrinology","Receptor","Cannabinoid receptor","Internal medicine","Epithelium","Gut flora","Cell biology","Immunology","Medicine","Biochemistry","Permeability (electromagnetism)","Diet-induced obesity","Gut Barrier","Cannabinoid Receptor-1","Tight Junction Proteins","Diet, High-Fat","Article","Mice, Inbred C57BL","Mice","Receptor, Cannabinoid, CB1","Animals","Obesity","Intestinal Mucosa","Receptors, Cannabinoid","Endocannabinoids"],"sdg_mappings":[{"sdg_number":2,"sdg_label":"2. 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