Mediobasal Hypothalamic Overexpression of Deptor Protects Against High-Fat Diet-Induced Obesity

•Systemic (brain and peripheral) overexpression of DEPTOR promotes activity and improves glucose homeostasis.•Systemic (brain and peripheral) overexpression of DEPTOR protects againts high-fat diet-induced obesity and metabolic alterations.•Deptor is widely expressed in the mouse brain, with a high expression in the mediobasal hypothalamus (MBH), a key region of the brain that regulates energy balance.•MBH-specific DEPTOR overexpression improves glucose metabolism and protects mice against obesity.•MBH-specific DEPTOR overexpression promotes hypothalamic Akt/PKB signaling.