Clinica Medica “Cesare Frugoni”, Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy
Fabiola Bovenga
Clinica Medica “Cesare Frugoni”, Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy
Marilidia Piglionica
Clinica Medica “Cesare Frugoni”, Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy
Elena Piccinin
Clinica Medica “Cesare Frugoni”, Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy; Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy
Marica Cariello
Clinica Medica “Cesare Frugoni”, Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy
Maria Arconzo
Clinica Medica “Cesare Frugoni”, Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy
Claudia Peres
Clinica Medica “Cesare Frugoni”, Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy
Paola Antonia Corsetto
Department of Pharmacological and Biomolecular Sciences, University of Milan, Via D. Trentacoste 2, 20133 Milan, Italy
Angela Maria Rizzo
Department of Pharmacological and Biomolecular Sciences, University of Milan, Via D. Trentacoste 2, 20133 Milan, Italy
Marta Ballanti
Center for Atherosclerosis, Policlinico Tor Vergata, 00133 Rome, Italy
Rossella Menghini
Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
Geltrude Mingrone
Department of Internal Medicine, Catholic University, Rome, Italy; Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Diabetes and Nutritional Sciences, Hodgkin Building, Guy's Campus, King's College London, London, UK
Philippe Lefebvre
Université Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, F-59000 Lille, France
Bart Staels
Université Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, F-59000 Lille, France
Takuji Shirasawa
Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan
Carlo Sabbà
Clinica Medica “Cesare Frugoni”, Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy
Gaetano Villani
Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy
Massimo Federici
Center for Atherosclerosis, Policlinico Tor Vergata, 00133 Rome, Italy; Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
Antonio Moschetta
Clinica Medica “Cesare Frugoni”, Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy; IRCCS Istituto Tumori “Giovanni Paolo II”, Viale O. Flacco 65, 70124 Bari, Italy; Corresponding author
Summary: Compelling evidence support an involvement of oxidative stress and intestinal inflammation as early events in the predisposition and development of obesity and its related comorbidities. Here, we show that deficiency of the major mitochondrial antioxidant enzyme superoxide dismutase 2 (SOD2) in the gastrointestinal tract drives spontaneous obesity. Intestinal epithelium-specific Sod2 ablation in mice induced adiposity and inflammation via phospholipase A2 (PLA2) activation and increased release of omega-6 polyunsaturated fatty acid arachidonic acid. Remarkably, this obese phenotype was rescued when fed an essential fatty acid-deficient diet, which abrogates de novo biosynthesis of arachidonic acid. Data from clinical samples revealed that the negative correlation between intestinal Sod2 mRNA levels and obesity features appears to be conserved between mice and humans. Collectively, our findings suggest a role of intestinal Sod2 levels, PLA2 activity, and arachidonic acid in obesity presenting new potential targets of therapeutic interest in the context of this metabolic disorder.
