The brown adipose tissue (BAT) is known to regulate whole body energy expenditure through sympathetically activated thermogenesis and therefore protect the body against diet-induced obesity [ 20 ]. Prompted by the altered energy expenditure in metabolic stress condition including HFD and age in SF-1 KO mice, we sought to explore the molecular mechanism regulating energy expenditure by assaying various genes mediating thermogenesis in the BAT. The KO mice showed significantly reduced levels of uncoupling protein 1 (UCP1), beta 3-adrenergic receptor (β3AR), and peroxisome proliferator-activated receptor γ (PPARγ) indicating that SF-1 might be important for the regulation of thermogenesis through activation of BAT especially in metabolic stress condition including high fat diet and aging ( Fig 5A–5C ). It has been suggested that the VMH expresses high level of vesicular glutamate transporter 2 (Vglut2) and the deletion of Vglut2 in SF-1 neurons was reported to induce obesity under high fat diet associated with hyperphagia and blunted response to hypoglycemia [ 14 ]. In the current study, SF-1 deletion in the VMH also induced hyperphagia, hormonal dysregulation and subsequent obesity development. Therefore, we wondered whether deleting SF-1 in the VMH had any effect on Vglut2 expression. Interestingly, we found a marked reduction in Vglut2 expression specifically in the VMH of SF-1 KO mice ( Fig 5D ) suggesting that the obese phenotype and hyperphagia observed in SF-1 KO mice might be, at least in part, linked to the change in Vglut2 expression.