These recent findings suggest that CD137-CD137L signaling mediates microglia-astrocyte crosstalk in hypothalamic inflammatory responses under obese conditions, and CD137L reverse signaling in microglia might be a potential therapeutic target for the suppression of obesity-induced hypothalamic inflammation and related metabolic diseases. The gene discussed is TNFRSF9; the disease is obesity due to melanocortin 4 receptor deficiency.