Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a Friedreich’s ataxia mouse model
Summary: Friedreich’s ataxia (FA) is a neurodegenerative disease resulting from a mutation in the FXN gene, leading to mitochondrial frataxin deficiency. FA patients exhibit increased visceral adiposity, inflammation, and heightened diabetes risk, negatively affecting prognosis. We investigated visc...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422301790X |
| _version_ | 1797647877808324608 |
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| author | Riccardo Turchi Francesca Sciarretta Veronica Ceci Marta Tiberi Matteo Audano Silvia Pedretti Concetta Panebianco Valentina Nesci Valerio Pazienza Alberto Ferri Simone Carotti Valerio Chiurchiù Nico Mitro Daniele Lettieri-Barbato Katia Aquilano |
| author_facet | Riccardo Turchi Francesca Sciarretta Veronica Ceci Marta Tiberi Matteo Audano Silvia Pedretti Concetta Panebianco Valentina Nesci Valerio Pazienza Alberto Ferri Simone Carotti Valerio Chiurchiù Nico Mitro Daniele Lettieri-Barbato Katia Aquilano |
| author_sort | Riccardo Turchi |
| collection | DOAJ |
| description | Summary: Friedreich’s ataxia (FA) is a neurodegenerative disease resulting from a mutation in the FXN gene, leading to mitochondrial frataxin deficiency. FA patients exhibit increased visceral adiposity, inflammation, and heightened diabetes risk, negatively affecting prognosis. We investigated visceral white adipose tissue (vWAT) in a murine model (KIKO) to understand its role in FA-related metabolic complications. RNA-seq analysis revealed altered expression of inflammation, angiogenesis, and fibrosis genes. Diabetes-like traits, including larger adipocytes, immune cell infiltration, and increased lactate production, were observed in vWAT. FXN downregulation in cultured adipocytes mirrored vWAT diabetes-like features, showing metabolic shifts toward glycolysis and lactate production. Metagenomic analysis indicated a reduction in fecal butyrate-producing bacteria, known to exert antidiabetic effects. A butyrate-enriched diet restrained vWAT abnormalities and mitigated diabetes features in KIKO mice. Our work emphasizes the role of vWAT in FA-related metabolic issues and suggests butyrate as a safe and promising adjunct for FA management. |
| first_indexed | 2024-03-11T15:23:00Z |
| format | Article |
| id | doaj.art-3c5148320c0b4e6788f36ea29e2d36bc |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-11T15:23:00Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-3c5148320c0b4e6788f36ea29e2d36bc2023-10-28T05:08:10ZengElsevieriScience2589-00422023-10-012610107713Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a Friedreich’s ataxia mouse modelRiccardo Turchi0Francesca Sciarretta1Veronica Ceci2Marta Tiberi3Matteo Audano4Silvia Pedretti5Concetta Panebianco6Valentina Nesci7Valerio Pazienza8Alberto Ferri9Simone Carotti10Valerio Chiurchiù11Nico Mitro12Daniele Lettieri-Barbato13Katia Aquilano14Department Biology, University of Rome Tor Vergata, Rome, ItalyIRCCS Fondazione Santa Lucia, Rome, ItalyPhD Program in Evolutionary Biology and Ecology, Department of Biology, University of Rome Tor Vergata, Rome, ItalyLaboratory of Resolution of Neuroinflammation, IRCCS Fondazione Santa Lucia, Rome, ItalyDiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, ItalyDiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, ItalyGastroenterology Unit Fondazione IRCSS “Casa Sollievo della Sofferenza” Hospital San Giovanni Rotondo (FG)-ItalyDepartment of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; Division of Experimental Neuroscience, IRCCS Fondazione Santa Lucia, Rome, ItalyGastroenterology Unit Fondazione IRCSS “Casa Sollievo della Sofferenza” Hospital San Giovanni Rotondo (FG)-ItalyDivision of Experimental Neuroscience, IRCCS Fondazione Santa Lucia, Rome, Italy; Institute of Traslational Pharmacology, IFT-CNR, Rome, ItalyMicroscopic and Ultrastructural Anatomy Research Unit, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy; Predictive Molecular Diagnostics, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyLaboratory of Resolution of Neuroinflammation, IRCCS Fondazione Santa Lucia, Rome, Italy; Institute of Traslational Pharmacology, IFT-CNR, Rome, ItalyDiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy; Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, ItalyDepartment Biology, University of Rome Tor Vergata, Rome, Italy; IRCCS Fondazione Santa Lucia, Rome, Italy; Corresponding authorDepartment Biology, University of Rome Tor Vergata, Rome, Italy; Corresponding authorSummary: Friedreich’s ataxia (FA) is a neurodegenerative disease resulting from a mutation in the FXN gene, leading to mitochondrial frataxin deficiency. FA patients exhibit increased visceral adiposity, inflammation, and heightened diabetes risk, negatively affecting prognosis. We investigated visceral white adipose tissue (vWAT) in a murine model (KIKO) to understand its role in FA-related metabolic complications. RNA-seq analysis revealed altered expression of inflammation, angiogenesis, and fibrosis genes. Diabetes-like traits, including larger adipocytes, immune cell infiltration, and increased lactate production, were observed in vWAT. FXN downregulation in cultured adipocytes mirrored vWAT diabetes-like features, showing metabolic shifts toward glycolysis and lactate production. Metagenomic analysis indicated a reduction in fecal butyrate-producing bacteria, known to exert antidiabetic effects. A butyrate-enriched diet restrained vWAT abnormalities and mitigated diabetes features in KIKO mice. Our work emphasizes the role of vWAT in FA-related metabolic issues and suggests butyrate as a safe and promising adjunct for FA management.http://www.sciencedirect.com/science/article/pii/S258900422301790XPharmacologyNatural sciencesBiological sciencesNeuroscience |
| spellingShingle | Riccardo Turchi Francesca Sciarretta Veronica Ceci Marta Tiberi Matteo Audano Silvia Pedretti Concetta Panebianco Valentina Nesci Valerio Pazienza Alberto Ferri Simone Carotti Valerio Chiurchiù Nico Mitro Daniele Lettieri-Barbato Katia Aquilano Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a Friedreich’s ataxia mouse model iScience Pharmacology Natural sciences Biological sciences Neuroscience |
| title | Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a Friedreich’s ataxia mouse model |
| title_full | Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a Friedreich’s ataxia mouse model |
| title_fullStr | Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a Friedreich’s ataxia mouse model |
| title_full_unstemmed | Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a Friedreich’s ataxia mouse model |
| title_short | Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a Friedreich’s ataxia mouse model |
| title_sort | butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a friedreich s ataxia mouse model |
| topic | Pharmacology Natural sciences Biological sciences Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S258900422301790X |
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