Selective ablation of hypothalamic POMC-expressing neurons leads to hyperphagia and weight gain

The pro-opiomelanocortin (POMC) gene is expressed in a subset of hypothalamic and hindbrain neurons and in pituitary melanotrophs and corticotrophs. POMC neurons in the arcuate nucleus (ARC) of the hypothalamus have been shown to play an important role in the regulation of energy homeostasis by integrating peripheral hormonal signals such as Leptin and Insulin in order to promote negative energy balance. As expected, POMC knockout mice display an obese phenotype, adrenal insufficiency and alterations in pigmentation. Recently, we were able to demonstrate that acute systemic ablation of POMC-expressing cells in adult mice results in hyperphagia and obesity accompanied by severe hypocortisolism. With the methods employed in previous studies it was impossible to separate the effect of hypothalamic POMC cell ablation from the effect caused by systemic ablation also affecting the pituitary gland. Here we demonstrate a procedure to selectively ablate the hypothalamic subset of POMC-expressing neurons without influencing pituitary POMC expression, leading to hyperphagia and weight gain.