TNF and obesity due to melanocortin 4 receptor deficiency: Exposing B cells from lean individuals to leptin reproduced this dysfunctional phenotype by increasing phospho-STAT3 (driving TNF-α production) and reducing phospho-AMPK (an upstream regulator of p38 MAPK and E47), indicating that high leptin contributes to obesity-associated B cell inflammation and impaired vaccine responses [183].