Nobiletin restores the intestinal barrier of HFD-induced obese mice by promoting MHC-II expression and lipid metabolism
Abstract The incidence of obesity is increasing annually worldwide. A high-fat diet (HFD) causes intestinal barrier damage, but effective interventions are currently unavailable. Our previous work demonstrated the therapeutic effect of nobiletin on obese mice; thus, we hypothesized that nobiletin co...
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BMC
2025-01-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-025-01072-1 |
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| author | Ni Yang Yue-Shan Pang Yali Zheng Yan-Ju Gong Wei-Jun Ding |
| author_facet | Ni Yang Yue-Shan Pang Yali Zheng Yan-Ju Gong Wei-Jun Ding |
| author_sort | Ni Yang |
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| description | Abstract The incidence of obesity is increasing annually worldwide. A high-fat diet (HFD) causes intestinal barrier damage, but effective interventions are currently unavailable. Our previous work demonstrated the therapeutic effect of nobiletin on obese mice; thus, we hypothesized that nobiletin could reverse HFD-induced damage to the intestinal barrier. Male C57BL/6 J mice were orally administered nobiletin for 14 d. After identification, the obese mice were equally divided into three groups: the HFD group, the low-dose (NOL, 100 mg/kg/d) group and the high-dose nobiletin (NOH, 200 mg/kg/d) group. A normal control group (CON) was also included. Hematoxylin and eosin (HE) staining and immunofluorescence were used to observe the intestinal barrier. RT-qPCR was used to determine the transcriptomic levels of genes involved in intestinal barrier integrity and lipid metabolism. The results revealed that intestinal tight proteins, including ZO-1 and Occludin, were significantly reduced in HFD-fed mice but markedly restored after nobiletin intervention, particularly in NOH mice. Improvements in the intestinal barrier and lipid metabolism associated with major histocompatibility complex class II (MHC-II) and relevant elements were revealed after nobiletin intervention. Enrichment analysis revealed that MHC-II plays an important role in the restoration of the intestinal barrier. Taken together, nobiletin restored intestinal barrier integrity and lipid metabolism by regulating MHC-II expression. |
| format | Article |
| id | doaj-art-5237f0ef7c6e4f5997a468db013721bc |
| institution | Kabale University |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Molecular Medicine |
| spelling | doaj-art-5237f0ef7c6e4f5997a468db013721bc2025-02-02T12:29:25ZengBMCMolecular Medicine1528-36582025-01-013111910.1186/s10020-025-01072-1Nobiletin restores the intestinal barrier of HFD-induced obese mice by promoting MHC-II expression and lipid metabolismNi Yang0Yue-Shan Pang1Yali Zheng2Yan-Ju Gong3Wei-Jun Ding4Department of Fundamental Medicine, Chengdu University of Traditional Chinese MedicineDepartment of Fundamental Medicine, Chengdu University of Traditional Chinese MedicineDepartment of Fundamental Medicine, Chengdu University of Traditional Chinese MedicineDepartment of Fundamental Medicine, Chengdu University of Traditional Chinese MedicineDepartment of Fundamental Medicine, Chengdu University of Traditional Chinese MedicineAbstract The incidence of obesity is increasing annually worldwide. A high-fat diet (HFD) causes intestinal barrier damage, but effective interventions are currently unavailable. Our previous work demonstrated the therapeutic effect of nobiletin on obese mice; thus, we hypothesized that nobiletin could reverse HFD-induced damage to the intestinal barrier. Male C57BL/6 J mice were orally administered nobiletin for 14 d. After identification, the obese mice were equally divided into three groups: the HFD group, the low-dose (NOL, 100 mg/kg/d) group and the high-dose nobiletin (NOH, 200 mg/kg/d) group. A normal control group (CON) was also included. Hematoxylin and eosin (HE) staining and immunofluorescence were used to observe the intestinal barrier. RT-qPCR was used to determine the transcriptomic levels of genes involved in intestinal barrier integrity and lipid metabolism. The results revealed that intestinal tight proteins, including ZO-1 and Occludin, were significantly reduced in HFD-fed mice but markedly restored after nobiletin intervention, particularly in NOH mice. Improvements in the intestinal barrier and lipid metabolism associated with major histocompatibility complex class II (MHC-II) and relevant elements were revealed after nobiletin intervention. Enrichment analysis revealed that MHC-II plays an important role in the restoration of the intestinal barrier. Taken together, nobiletin restored intestinal barrier integrity and lipid metabolism by regulating MHC-II expression.https://doi.org/10.1186/s10020-025-01072-1High-fat diet (HFD)NobiletinIntestinal barrierMajor histocompatibility complex class-II (MHC-II)Lipid metabolism |
| spellingShingle | Ni Yang Yue-Shan Pang Yali Zheng Yan-Ju Gong Wei-Jun Ding Nobiletin restores the intestinal barrier of HFD-induced obese mice by promoting MHC-II expression and lipid metabolism Molecular Medicine High-fat diet (HFD) Nobiletin Intestinal barrier Major histocompatibility complex class-II (MHC-II) Lipid metabolism |
| title | Nobiletin restores the intestinal barrier of HFD-induced obese mice by promoting MHC-II expression and lipid metabolism |
| title_full | Nobiletin restores the intestinal barrier of HFD-induced obese mice by promoting MHC-II expression and lipid metabolism |
| title_fullStr | Nobiletin restores the intestinal barrier of HFD-induced obese mice by promoting MHC-II expression and lipid metabolism |
| title_full_unstemmed | Nobiletin restores the intestinal barrier of HFD-induced obese mice by promoting MHC-II expression and lipid metabolism |
| title_short | Nobiletin restores the intestinal barrier of HFD-induced obese mice by promoting MHC-II expression and lipid metabolism |
| title_sort | nobiletin restores the intestinal barrier of hfd induced obese mice by promoting mhc ii expression and lipid metabolism |
| topic | High-fat diet (HFD) Nobiletin Intestinal barrier Major histocompatibility complex class-II (MHC-II) Lipid metabolism |
| url | https://doi.org/10.1186/s10020-025-01072-1 |
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