A Lipidomics- and Transcriptomics-Based Analysis of the Intestine of Genetically Obese (<i>ob/ob</i>) and Diabetic (<i>db/db</i>) Mice: Links with Inflammation and Gut Microbiota
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,...
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MDPI AG
2023-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/3/411 |
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| author | Francesco Suriano Claudia Manca Nicolas Flamand Matthias Van Hul Nathalie M. Delzenne Cristoforo Silvestri Patrice D. Cani Vincenzo Di Marzo |
| author_facet | Francesco Suriano Claudia Manca Nicolas Flamand Matthias Van Hul Nathalie M. Delzenne Cristoforo Silvestri Patrice D. Cani Vincenzo Di Marzo |
| author_sort | Francesco Suriano |
| collection | DOAJ |
| description | 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 (<i>ob/ob</i>) and diabetic (<i>db/db</i>) 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 <i>db/db</i> mice. In particular, the duodenal levels of several 2-monoacylglycerols and <i>N</i>-acylethanolamines were increased and decreased, respectively, in <i>db/db</i> 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 <i>db/db</i> mice present a higher inflammatory state in the intestine as compared to <i>ob/ob</i> 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. |
| first_indexed | 2024-03-11T09:48:50Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T09:48:50Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-2728c7aac158414481789237c6009ec32023-11-16T16:21:15ZengMDPI AGCells2073-44092023-01-0112341110.3390/cells12030411A Lipidomics- and Transcriptomics-Based Analysis of the Intestine of Genetically Obese (<i>ob/ob</i>) and Diabetic (<i>db/db</i>) Mice: Links with Inflammation and Gut MicrobiotaFrancesco Suriano0Claudia Manca1Nicolas Flamand2Matthias Van Hul3Nathalie M. Delzenne4Cristoforo Silvestri5Patrice D. Cani6Vincenzo Di Marzo7Metabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), UCLouvain, Université Catholique de Louvain, Av. E. Mounier, 73 B1.73.11, 1200 Brussels, BelgiumQuebec Heart and Lung Institute Research Centre, Université Laval, Quebec City, QC G1V 0A6, CanadaQuebec Heart and Lung Institute Research Centre, Université Laval, Quebec City, QC G1V 0A6, CanadaMetabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), UCLouvain, Université Catholique de Louvain, Av. E. Mounier, 73 B1.73.11, 1200 Brussels, BelgiumMetabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), UCLouvain, Université Catholique de Louvain, Av. E. Mounier, 73 B1.73.11, 1200 Brussels, BelgiumQuebec Heart and Lung Institute Research Centre, Université Laval, Quebec City, QC G1V 0A6, CanadaMetabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), UCLouvain, Université Catholique de Louvain, Av. E. Mounier, 73 B1.73.11, 1200 Brussels, BelgiumQuebec Heart and Lung Institute Research Centre, Université Laval, Quebec City, QC G1V 0A6, CanadaObesity 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 (<i>ob/ob</i>) and diabetic (<i>db/db</i>) 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 <i>db/db</i> mice. In particular, the duodenal levels of several 2-monoacylglycerols and <i>N</i>-acylethanolamines were increased and decreased, respectively, in <i>db/db</i> 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 <i>db/db</i> mice present a higher inflammatory state in the intestine as compared to <i>ob/ob</i> 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.https://www.mdpi.com/2073-4409/12/3/411lipidomicstranscriptomicsendocannabinoidsenzymesintestineobesity |
| spellingShingle | Francesco Suriano Claudia Manca Nicolas Flamand Matthias Van Hul Nathalie M. Delzenne Cristoforo Silvestri Patrice D. Cani Vincenzo Di Marzo A Lipidomics- and Transcriptomics-Based Analysis of the Intestine of Genetically Obese (<i>ob/ob</i>) and Diabetic (<i>db/db</i>) Mice: Links with Inflammation and Gut Microbiota Cells lipidomics transcriptomics endocannabinoids enzymes intestine obesity |
| title | A Lipidomics- and Transcriptomics-Based Analysis of the Intestine of Genetically Obese (<i>ob/ob</i>) and Diabetic (<i>db/db</i>) Mice: Links with Inflammation and Gut Microbiota |
| title_full | A Lipidomics- and Transcriptomics-Based Analysis of the Intestine of Genetically Obese (<i>ob/ob</i>) and Diabetic (<i>db/db</i>) Mice: Links with Inflammation and Gut Microbiota |
| title_fullStr | A Lipidomics- and Transcriptomics-Based Analysis of the Intestine of Genetically Obese (<i>ob/ob</i>) and Diabetic (<i>db/db</i>) Mice: Links with Inflammation and Gut Microbiota |
| title_full_unstemmed | A Lipidomics- and Transcriptomics-Based Analysis of the Intestine of Genetically Obese (<i>ob/ob</i>) and Diabetic (<i>db/db</i>) Mice: Links with Inflammation and Gut Microbiota |
| title_short | A Lipidomics- and Transcriptomics-Based Analysis of the Intestine of Genetically Obese (<i>ob/ob</i>) and Diabetic (<i>db/db</i>) Mice: Links with Inflammation and Gut Microbiota |
| title_sort | lipidomics and transcriptomics based analysis of the intestine of genetically obese i ob ob i and diabetic i db db i mice links with inflammation and gut microbiota |
| topic | lipidomics transcriptomics endocannabinoids enzymes intestine obesity |
| url | https://www.mdpi.com/2073-4409/12/3/411 |
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