Helminth infection-induced Resistin-Like Molecule Alpha (RELMα) protects from diet-induced obesity 4159

Abstract Description Resistin-Like Molecule Alpha (RELMα), a macrophage-secreted protein, is crucial for immunomodulation in type 2 immune responses, such as parasitic helminth infections. Obesity, a leading cause of preventable death, exhibits a pro-inflammatory Th1 environment with M1-like macrophages in visceral fat, while healthy adipose tissue has an anti-inflammatory Th2 environment with M2-like macrophages. Our lab demonstrated that RELMα protects naive mice against diet-induced obesity via induction of M2 macrophages in visceral adipose tissue. We hypothesize that elevating macrophage-derived RELMα levels through helminth infection could protect from obesity and metabolic dysfunction. We employed two complementary methods to increase macrophage-derived RELMα: helminth infection and lentiviral-induced RELMα overexpression. Mice were fed a western diet for 10–14 weeks, followed by infection with Nippostrongylus brasiliensis. RELMα lentiviral overexpression in bone marrow-derived macrophages (BMDMs) allowed investigation of effects on macrophage polarization. Helminth-induced RELMα reduces weight gain and adiposity, enhances glucose tolerance, and promotes anti-inflammatory changes in visceral fat. RELMα-overexpressing macrophages show enhanced M2-like responses to Th2 stimuli and suppressed M1-like responses to Th1 stimuli. These findings suggest that macrophage-specific RELMα overexpression could be a therapeutic strategy for diet-induced obesity and related comorbidities. Funding Sources NIH1RO1AI135195-01 NIH3R01AI153195-03S1 Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)