LAUSR

Significance Anorexia nervosa is a life-threatening psychiatric illness with poorly understood cellular and molecular mechanisms and limited treatment options. Emerging evidence points to the importance of hypothalamic agouti-related peptide (AgRP) neurons in anorexia nervosa, but the underlying molecular mechanisms linking AgRP neurons to this illness have remained ill-defined. Here, we show that Bobcat339, a synthetic small molecule that controls TET3 in AgRP neurons, is able to mitigate anorexia nervosa and associated anxiety/depressive behaviors in a murine model. We show that Bobcat339 acts to destabilize TET3 protein in AgRP neurons and that this regulation is conserved in human and mouse cells. We propose that Bobcat339 should be pursued as a therapeutic for anorexia nervosa and perhaps cancer-induced anorexia and associated mood disorders.