Melanocortin-3 receptors expressed in Nkx2.1(+ve) neurons are sufficient for controlling appetitive responses to hypocaloric conditioning

作者：Girardet Clemence; Mavrikaki Maria M; Stevens Joseph R; Miller Courtney A; Marks Daniel L; Butler Andrew A

来源：Scientific Reports, 2017, 7(1): 44444.

DOI：10.1038/srep44444

<jats:title>Abstract</jats:title><jats:p>Melanocortin-3 receptors (MC3R) have a contextual role in appetite control that is amplified with hypocaloric conditioning. C57BL/6J (B6) mice subjected to hypocaloric feeding schedules (HFS) exhibit compulsive behavioral responses involving food anticipatory activity (FAA) and caloric loading following food access. These homeostatic responses to calorie-poor environs are attenuated in B6 mice in which Mc3r transcription is suppressed by a lox-stop-lox sequence in the 5’UTR (<jats:italic>Mc3r</jats:italic><jats:sup><jats:italic>TB/TB</jats:italic></jats:sup> ). Here, we report that optimization of caloric loading in B6 mice subject to HFS, characterized by increased meal size and duration, is not observed in <jats:italic>Mc3r</jats:italic><jats:sup><jats:italic>TB/TB</jats:italic></jats:sup> mice. Analysis of hypothalamic and neuroendocrine responses to HFS throughout the light-dark cycle suggests uncoupling of hypothalamic responses involving appetite-stimulating fasting-responsive hypothalamic neurons expressing agouti-related peptide (AgRP) and neuropeptide Y (Npy). Rescuing Mc3rs expression in Nkx2.1(+ve) neurons is sufficient to restore normal hypothalamic responses to negative energy balance. In addition, <jats:italic>Mc3rs</jats:italic> expressed in Nkx2.1(+ve) neurons are also sufficient to restore FAA and caloric loading of B6 mice subjected to HFS. In summary, MC3Rs expressed in Nkx2.1(+ve) neurons are sufficient to coordinate hypothalamic response and expression of compulsive behavioral responses involving meal anticipation and consumption of large meals during situations of prolonged negative energy balance.</jats:p>

• 出版日期2017-3-15