Tff3 Deficiency Differentially Affects the Morphology of Male and Female Intestines in a Long-Term High-Fat-Diet-Fed Mouse Model
Trefoil factor family protein 3 (Tff3) protects the gastrointestinal mucosa and has a complex mode of action in different tissues. Here, we aimed to determine the effect of Tff3 deficiency on intestinal tissues in a long-term high-fat-diet (HFD)-fed model. A novel congenic strain without additional...
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MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/22/16342 |
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| author | Kate Šešelja Iva Bazina Milka Vrecl Jessica Farger Martin Schicht Friedrich Paulsen Mirela Baus Lončar Tatjana Pirman |
| author_facet | Kate Šešelja Iva Bazina Milka Vrecl Jessica Farger Martin Schicht Friedrich Paulsen Mirela Baus Lončar Tatjana Pirman |
| author_sort | Kate Šešelja |
| collection | DOAJ |
| description | Trefoil factor family protein 3 (Tff3) protects the gastrointestinal mucosa and has a complex mode of action in different tissues. Here, we aimed to determine the effect of Tff3 deficiency on intestinal tissues in a long-term high-fat-diet (HFD)-fed model. A novel congenic strain without additional metabolically relevant mutations (<i>Tff3</i>-/-/C57Bl6NCrl strain, male and female) was used. Wild type (Wt) and Tff3-deficient mice of both sexes were fed a HFD for 36 weeks. Long-term feeding of a HFD induces different effects on the intestinal structure of Tff3-deficient male and female mice. For the first time, we found sex-specific differences in duodenal morphology. HFD feeding reduced microvilli height in Tff3-deficient females compared to that in Wt females, suggesting a possible effect on microvillar actin filament dynamics. These changes could not be attributed to genes involved in ER and oxidative stress, apoptosis, or inflammation. Tff3-deficient males exhibited a reduced cecal crypt depth compared to that of Wt males, but this was not the case in females. Microbiome-related short-chain fatty acid content was not affected by Tff3 deficiency in HFD-fed male or female mice. Sex-related differences due to Tff3 deficiency imply the need to consider both sexes in future studies on the role of Tff in intestinal function. |
| first_indexed | 2024-03-09T16:45:10Z |
| format | Article |
| id | doaj.art-92f4c30210124c7d9b4a82a8322fc741 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:45:10Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-92f4c30210124c7d9b4a82a8322fc7412023-11-24T14:47:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124221634210.3390/ijms242216342Tff3 Deficiency Differentially Affects the Morphology of Male and Female Intestines in a Long-Term High-Fat-Diet-Fed Mouse ModelKate Šešelja0Iva Bazina1Milka Vrecl2Jessica Farger3Martin Schicht4Friedrich Paulsen5Mirela Baus Lončar6Tatjana Pirman7Department of Molecular Medicine, Ruđer Bošković Institute, Bjenička 54, 10 000 Zagreb, CroatiaDepartment of Molecular Medicine, Ruđer Bošković Institute, Bjenička 54, 10 000 Zagreb, CroatiaInstitute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, Gerbičeva 60, 1000 Ljubljana, SloveniaInstitute of Functional and Clinical Anatomy, Faculty of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, GermanyInstitute of Functional and Clinical Anatomy, Faculty of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, GermanyInstitute of Functional and Clinical Anatomy, Faculty of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, GermanyDepartment of Molecular Medicine, Ruđer Bošković Institute, Bjenička 54, 10 000 Zagreb, CroatiaDepartment of Animal Science, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, 1000 Ljubljana, SloveniaTrefoil factor family protein 3 (Tff3) protects the gastrointestinal mucosa and has a complex mode of action in different tissues. Here, we aimed to determine the effect of Tff3 deficiency on intestinal tissues in a long-term high-fat-diet (HFD)-fed model. A novel congenic strain without additional metabolically relevant mutations (<i>Tff3</i>-/-/C57Bl6NCrl strain, male and female) was used. Wild type (Wt) and Tff3-deficient mice of both sexes were fed a HFD for 36 weeks. Long-term feeding of a HFD induces different effects on the intestinal structure of Tff3-deficient male and female mice. For the first time, we found sex-specific differences in duodenal morphology. HFD feeding reduced microvilli height in Tff3-deficient females compared to that in Wt females, suggesting a possible effect on microvillar actin filament dynamics. These changes could not be attributed to genes involved in ER and oxidative stress, apoptosis, or inflammation. Tff3-deficient males exhibited a reduced cecal crypt depth compared to that of Wt males, but this was not the case in females. Microbiome-related short-chain fatty acid content was not affected by Tff3 deficiency in HFD-fed male or female mice. Sex-related differences due to Tff3 deficiency imply the need to consider both sexes in future studies on the role of Tff in intestinal function.https://www.mdpi.com/1422-0067/24/22/16342trefoil peptide 3duodenumcecumhigh-fat dietoxidative stressER stress |
| spellingShingle | Kate Šešelja Iva Bazina Milka Vrecl Jessica Farger Martin Schicht Friedrich Paulsen Mirela Baus Lončar Tatjana Pirman Tff3 Deficiency Differentially Affects the Morphology of Male and Female Intestines in a Long-Term High-Fat-Diet-Fed Mouse Model International Journal of Molecular Sciences trefoil peptide 3 duodenum cecum high-fat diet oxidative stress ER stress |
| title | Tff3 Deficiency Differentially Affects the Morphology of Male and Female Intestines in a Long-Term High-Fat-Diet-Fed Mouse Model |
| title_full | Tff3 Deficiency Differentially Affects the Morphology of Male and Female Intestines in a Long-Term High-Fat-Diet-Fed Mouse Model |
| title_fullStr | Tff3 Deficiency Differentially Affects the Morphology of Male and Female Intestines in a Long-Term High-Fat-Diet-Fed Mouse Model |
| title_full_unstemmed | Tff3 Deficiency Differentially Affects the Morphology of Male and Female Intestines in a Long-Term High-Fat-Diet-Fed Mouse Model |
| title_short | Tff3 Deficiency Differentially Affects the Morphology of Male and Female Intestines in a Long-Term High-Fat-Diet-Fed Mouse Model |
| title_sort | tff3 deficiency differentially affects the morphology of male and female intestines in a long term high fat diet fed mouse model |
| topic | trefoil peptide 3 duodenum cecum high-fat diet oxidative stress ER stress |
| url | https://www.mdpi.com/1422-0067/24/22/16342 |
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