This study has provided advance in the understanding of hypothalamic Fezf1 and BDNF biology by showing that: i, VMH Fezf1 neurons are an important source of BDNF in the hypothalamus; ii, Fezf1 neurons project to key regions involved in the regulation of metabolism and locomotor activity; iii, the knockdown of Bdnf specifically in Fezf1 neurons results in a sexual dimorphic phenotype characterized by the protection against diet-induced obesity in females and improved BAT thermogenesis in males. This evidence concerns the gene BDNF and obesity disorder.