Sex differences in diet-induced MASLD – are female mice naturally protected?
Males suffer more often from profibrotic changes in liver than females. The underlying mechanism for this sex difference in the prevalence and manifestation of Metabolic dysfunction-associated Steatotic Liver Disease (MASLD) is not yet completely known. We studied male and female mice that were indu...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2025.1567573/full |
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| author | Jana Meyer Ana Mendes Teixeira Sandy Richter Dean P. Larner Asifuddin Syed Nora Klöting Madlen Matz-Soja Susanne Gaul Susanne Gaul Anja Barnikol-Oettler Wieland Kiess Diana Le Duc Diana Le Duc Melanie Penke Antje Garten |
| author_facet | Jana Meyer Ana Mendes Teixeira Sandy Richter Dean P. Larner Asifuddin Syed Nora Klöting Madlen Matz-Soja Susanne Gaul Susanne Gaul Anja Barnikol-Oettler Wieland Kiess Diana Le Duc Diana Le Duc Melanie Penke Antje Garten |
| author_sort | Jana Meyer |
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| description | Males suffer more often from profibrotic changes in liver than females. The underlying mechanism for this sex difference in the prevalence and manifestation of Metabolic dysfunction-associated Steatotic Liver Disease (MASLD) is not yet completely known. We studied male and female mice that were induced to develop MASLD by consuming a “fast food” diet (FFD) and assessed metabolic phenotype as well as liver histology and compared them with mice fed with a matched control diet (CD). Our aim was to check for sex-specific differences in MASLD development in a mouse model of diet-induced profibrotic changes in the liver. Our results demonstrate a clear difference in body weight, fat distribution and changes in liver tissue for male and female mice fed with FFD. We found that female mice stored lipids mainly in subcutaneous and visceral adipose tissue while males increased ectopic lipid accumulation in the liver which resulted in hepatomegaly and increased transforming growth factor β 1 (Tgfb1) and collagen I (Col1a1) expression concomitant to fibrosis development. This was absent in female mice. Analysis of estrogen receptor -α (Esr1) and -β (Esr2) expression revealed an upregulation of Esr2 in livers of male FFD-fed mice whereas in female liver tissue a higher expression in Esr1 could be observed. This study supports Esr1 and Esr2 as potential targets to reverse negative effects of diet-induced profibrotic changes in the liver. |
| format | Article |
| id | doaj-art-e0185c946cd8476c86e119493e2aa8b7 |
| institution | OA Journals |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj-art-e0185c946cd8476c86e119493e2aa8b72025-08-20T02:06:23ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-03-011610.3389/fendo.2025.15675731567573Sex differences in diet-induced MASLD – are female mice naturally protected?Jana Meyer0Ana Mendes Teixeira1Sandy Richter2Dean P. Larner3Asifuddin Syed4Nora Klöting5Madlen Matz-Soja6Susanne Gaul7Susanne Gaul8Anja Barnikol-Oettler9Wieland Kiess10Diana Le Duc11Diana Le Duc12Melanie Penke13Antje Garten14Center for Pediatric Research, University Hospital for Children and Adolescents, Leipzig University, Leipzig, GermanyCenter for Pediatric Research, University Hospital for Children and Adolescents, Leipzig University, Leipzig, GermanyCenter for Pediatric Research, University Hospital for Children and Adolescents, Leipzig University, Leipzig, GermanyDepartment of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham, United KingdomDepartment of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham, United KingdomHelmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) belonging to Helmholtz Center Munich at the University and University Hospital, Leipzig, GermanyDivision of Hepatology, Clinic and Polyclinic for Oncology, Gastroenterology, Hepatology, and Pneumology, University Hospital Leipzig, Leipzig, GermanyCenter for Pediatric Research, University Hospital for Children and Adolescents, Leipzig University, Leipzig, GermanyKlinik und Poliklinik für Kardiologie, University Hospital Leipzig, Leipzig University, Leipzig, GermanyCenter for Pediatric Research, University Hospital for Children and Adolescents, Leipzig University, Leipzig, GermanyCenter for Pediatric Research, University Hospital for Children and Adolescents, Leipzig University, Leipzig, GermanyInstitute of Human Genetics, University Medical Center Leipzig, Leipzig, GermanyDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, GermanyCenter for Pediatric Research, University Hospital for Children and Adolescents, Leipzig University, Leipzig, GermanyCenter for Pediatric Research, University Hospital for Children and Adolescents, Leipzig University, Leipzig, GermanyMales suffer more often from profibrotic changes in liver than females. The underlying mechanism for this sex difference in the prevalence and manifestation of Metabolic dysfunction-associated Steatotic Liver Disease (MASLD) is not yet completely known. We studied male and female mice that were induced to develop MASLD by consuming a “fast food” diet (FFD) and assessed metabolic phenotype as well as liver histology and compared them with mice fed with a matched control diet (CD). Our aim was to check for sex-specific differences in MASLD development in a mouse model of diet-induced profibrotic changes in the liver. Our results demonstrate a clear difference in body weight, fat distribution and changes in liver tissue for male and female mice fed with FFD. We found that female mice stored lipids mainly in subcutaneous and visceral adipose tissue while males increased ectopic lipid accumulation in the liver which resulted in hepatomegaly and increased transforming growth factor β 1 (Tgfb1) and collagen I (Col1a1) expression concomitant to fibrosis development. This was absent in female mice. Analysis of estrogen receptor -α (Esr1) and -β (Esr2) expression revealed an upregulation of Esr2 in livers of male FFD-fed mice whereas in female liver tissue a higher expression in Esr1 could be observed. This study supports Esr1 and Esr2 as potential targets to reverse negative effects of diet-induced profibrotic changes in the liver.https://www.frontiersin.org/articles/10.3389/fendo.2025.1567573/fullMAFLDNAFLDhigh fat dietadipose tissuefibrosisestrogen |
| spellingShingle | Jana Meyer Ana Mendes Teixeira Sandy Richter Dean P. Larner Asifuddin Syed Nora Klöting Madlen Matz-Soja Susanne Gaul Susanne Gaul Anja Barnikol-Oettler Wieland Kiess Diana Le Duc Diana Le Duc Melanie Penke Antje Garten Sex differences in diet-induced MASLD – are female mice naturally protected? Frontiers in Endocrinology MAFLD NAFLD high fat diet adipose tissue fibrosis estrogen |
| title | Sex differences in diet-induced MASLD – are female mice naturally protected? |
| title_full | Sex differences in diet-induced MASLD – are female mice naturally protected? |
| title_fullStr | Sex differences in diet-induced MASLD – are female mice naturally protected? |
| title_full_unstemmed | Sex differences in diet-induced MASLD – are female mice naturally protected? |
| title_short | Sex differences in diet-induced MASLD – are female mice naturally protected? |
| title_sort | sex differences in diet induced masld are female mice naturally protected |
| topic | MAFLD NAFLD high fat diet adipose tissue fibrosis estrogen |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1567573/full |
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