This study unveils endothelial TRPC1 as a critical regulator of metabolic homeostasis, with its dysfunction driving obesity-related metabolic complications through a cascade of “adipose tissue inflammation - thermogenic failure - metabolomic disruption.” However, the precise molecular pathways through which TRPC1 modulates vascular-immune interactions in adipose tissue, as well as the metabolic fate of GA12 in animals, warrant further investigation. Here, TRPC1 is linked to obesity disorder.