King's College London

Research portal

Enterocyte superoxide dismutase 2 deletion drives obesity

Research output: Contribution to journalArticlepeer-review

Oihane Garcia-Irigoyen, Fabiola Bovenga, Marilidia Piglionica, Elena Piccinin, Marica Cariello, Maria Arconzo, Claudia Peres, Paola Antonia Corsetto, Angela Maria Rizzo, Marta Ballanti, Rossella Menghini, Geltrude Mingrone, Philippe Lefebvre, Bart Staels, Takuji Shirasawa, Carlo Sabbà, Gaetano Villani, Massimo Federici, Antonio Moschetta

Original languageEnglish
Article number103707
JournaliScience
Volume25
Issue number1
Early online date7 Jan 2022
DOIs
Accepted/In press23 Dec 2021
E-pub ahead of print7 Jan 2022
Published21 Jan 2022

Bibliographical note

Funding Information: A. Moschetta is funded by: Interreg V-A Greece-Italy 2014-2020- SILVER WELLBEING , MIS5003627 ; MIUR-PRIN 2017 n.2017J3E2W2 ; EU-JPI HDL-INTIMIC–MIUR FATMAL ; MIUR-PON “R&I” 2014-2020 “ BIOMIS ” cod.ARS01_01220 ; P OR Puglia FESR–FSE 2014-2020,“ INNOMA ” cod. 4TCJLV4 . E. Piccinin is funded by PON- AIM 1853334 - Attività 2, linea 1. The authors acknowledge Smart Servier Medical Art ( http://smart.servier.com/ ) for providing comprehensive medical and biological figures for the graphical abstract. Funding Information: A. Moschetta is funded by: Interreg V-A Greece-Italy 2014-2020- SILVER WELLBEING, MIS5003627; MIUR-PRIN 2017 n.2017J3E2W2; EU-JPI HDL-INTIMIC?MIUR FATMAL; MIUR-PON ?R&I? 2014-2020 ?BIOMIS? cod.ARS01_01220; POR Puglia FESR?FSE2014-2020,?INNOMA?cod. 4TCJLV4. E. Piccinin is funded by PON-AIM 1853334 - Attivit? 2, linea 1. The authors acknowledge Smart Servier Medical Art (http://smart.servier.com/) for providing comprehensive medical and biological figures for the graphical abstract. OGI contributed to study design, performed experiments, analyzed the data, performed statistical analysis, and wrote the paper; FB generated the mouse colony; MP performed experiments and contributed to data analysis; EP performed experiments and contributed to data analysis and to manuscript final editing; CP and MC performed histology; MA contributed to perform the experiments; PAC and AMR performed lipidomic analysis; MF, MB, RM, GM, PL, and BS provided human samples, metabolomics, and transcriptomics data; TS provided SOD2flox mice; CS provided medical expertise and double checked the clinical relevance of the data; GV contributed to the writing of the paper; AM designed the study, supervised the project, and wrote the paper. All authors discussed the results and commented on the manuscript. The authors declare no competing interests. Publisher Copyright: © 2021 The Author(s)

Documents

King's Authors

Abstract

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.

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454