Abstract Overfeeding triggers homeostatic compensatory mechanisms that counteract weight gain. Here. we show that both lean and diet-induced obese (DIO) male mice exhibit a potent and prolonged inhibition of voluntary food intake following overfeeding-induced weight gain. We reveal that FGF21 is dispensable for this defense against weight gain. https://parisnaturalfoodes.shop/product-category/gf-potato-cheese-pierogi/