Utilizing an endothelial-specific TRPC1 knockout mouse model, this study reveals that TRPC1 deficiency, while not influencing the onset of obesity, exacerbates obesity-associated metabolic complications through the remodeling of the adipose tissue inflammatory microenvironment, impairment of thermogenic function, and disruption of serum metabolomic profiles. The gene discussed is TRPC1; the disease is obesity disorder.