Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a Friedreich’s ataxia mouse model
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
Affiliations
Riccardo Turchi
Department Biology, University of Rome Tor Vergata, Rome, Italy
Francesca Sciarretta
IRCCS Fondazione Santa Lucia, Rome, Italy
Veronica Ceci
PhD Program in Evolutionary Biology and Ecology, Department of Biology, University of Rome Tor Vergata, Rome, Italy
Marta Tiberi
Laboratory of Resolution of Neuroinflammation, IRCCS Fondazione Santa Lucia, Rome, Italy
Matteo Audano
DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy
Silvia Pedretti
DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy
Concetta Panebianco
Gastroenterology Unit Fondazione IRCSS “Casa Sollievo della Sofferenza” Hospital San Giovanni Rotondo (FG)-Italy
Valentina Nesci
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; Division of Experimental Neuroscience, IRCCS Fondazione Santa Lucia, Rome, Italy
Valerio Pazienza
Gastroenterology Unit Fondazione IRCSS “Casa Sollievo della Sofferenza” Hospital San Giovanni Rotondo (FG)-Italy
Alberto Ferri
Division of Experimental Neuroscience, IRCCS Fondazione Santa Lucia, Rome, Italy; Institute of Traslational Pharmacology, IFT-CNR, Rome, Italy
Simone Carotti
Microscopic 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, Italy
Valerio Chiurchiù
Laboratory of Resolution of Neuroinflammation, IRCCS Fondazione Santa Lucia, Rome, Italy; Institute of Traslational Pharmacology, IFT-CNR, Rome, Italy
Nico Mitro
DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy; Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
Daniele Lettieri-Barbato
Department Biology, University of Rome Tor Vergata, Rome, Italy; IRCCS Fondazione Santa Lucia, Rome, Italy; Corresponding author
Katia Aquilano
Department Biology, University of Rome Tor Vergata, Rome, Italy; Corresponding author
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.
