BackgroundObesity has been associated with depressive symptoms and impaired cognition, but the mechanisms underlying these relationships are not well understood. It is also not clear whether reducing adiposity reverses these behavioral outcomes. The current study tested the impact of bariatric surgery on depressive symptoms, cognition, and the brain; using a mediation model, we also examined whether the relationship between changes in adiposity after the surgery and those in regional thickness of the cerebral cortex are mediated by changes in low-grade inflammation (as indexed by C-reactive protein; CRP). MethodsA total of 18 bariatric patients completed 3 visits, including one baseline before the surgery and two post-surgery measurements acquired at 6- and 12-months post-surgery. Each visit consisted of a collection of fasting blood sample, magnetic resonance imaging of the brain and abdomen, and assessment of depressive symptoms and cognition. ResultsAfter surgery, we observed reductions of both visceral fat (p< 0.001) and subcutaneous fat (p< 0.001), less depressive symptoms (p< 0.001), improved verbal reasoning (p< 0.001), and reduced CRP (p< 0.001). Mediation analyses revealed that the relationships between the surgery-related changes in visceral fat and cortical thickness in depression-related regions are mediated by changes in CRP (ab=-.027, SE=.012, 95% CI [-.054, -,006]). ConclusionThese findings suggest that some of the beneficial effects of bariatric surgery on brain function and structure are due to a reduction of adiposity-related low-grade systemic inflammation.