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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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Autores principales: Šešelja, Kate, Bazina, Iva, Vrecl, Milka, Farger, Jessica, Schicht, Martin, Paulsen, Friedrich, Baus Lončar, Mirela, Pirman, Tatjana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671422/
https://www.ncbi.nlm.nih.gov/pubmed/38003531
http://dx.doi.org/10.3390/ijms242216342
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author Šešelja, Kate
Bazina, Iva
Vrecl, Milka
Farger, Jessica
Schicht, Martin
Paulsen, Friedrich
Baus Lončar, Mirela
Pirman, Tatjana
author_facet Šešelja, Kate
Bazina, Iva
Vrecl, Milka
Farger, Jessica
Schicht, Martin
Paulsen, Friedrich
Baus Lončar, Mirela
Pirman, Tatjana
author_sort Šešelja, Kate
collection PubMed
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 (Tff3-/-/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.
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spelling pubmed-106714222023-11-15 Tff3 Deficiency Differentially Affects the Morphology of Male and Female Intestines in a Long-Term High-Fat-Diet-Fed Mouse Model Šešelja, Kate Bazina, Iva Vrecl, Milka Farger, Jessica Schicht, Martin Paulsen, Friedrich Baus Lončar, Mirela Pirman, Tatjana Int J Mol Sci Article 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 (Tff3-/-/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. MDPI 2023-11-15 /pmc/articles/PMC10671422/ /pubmed/38003531 http://dx.doi.org/10.3390/ijms242216342 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Šešelja, Kate
Bazina, Iva
Vrecl, Milka
Farger, Jessica
Schicht, Martin
Paulsen, Friedrich
Baus Lončar, Mirela
Pirman, Tatjana
Tff3 Deficiency Differentially Affects the Morphology of Male and Female Intestines in a Long-Term High-Fat-Diet-Fed Mouse Model
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671422/
https://www.ncbi.nlm.nih.gov/pubmed/38003531
http://dx.doi.org/10.3390/ijms242216342
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