摘要：SummaryCompelling 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-specificSod2ablation 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 abrogatesde novobiosynthesis of arachidonic acid. Data from clinical samples revealed that the negative correlation between intestinalSod2mRNA levels and obesity features appears to be conserved between mice and humans. Collectively, our findings suggest a role of intestinalSod2levels, PLA2 activity, and arachidonic acid in obesity presenting new potential targets of therapeutic interest in the context of this metabolic disorder.Graphical abstractDisplay OmittedHighlights•Intestinal deletion of SOD2 drives spontaneous obesity and inflammation in mice•SOD2 deficiency promotes phospholipase A2 activation and arachidonic acid release•SOD2 ablation in enterocytes generates a pro-lipogenic phenotype•Inverse relation between intestinal SOD2 and obesity features is present in humansObesity medicine; Lipid; Molecular physiology
