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

Clémence Girardet, Maria M. Mavrikaki, Joseph R. Stevens, Courtney A. Miller, Daniel Marks, Andrew A. Butler

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Abstract

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 (Mc3r TB/TB). 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 Mc3r TB/TB 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, Mc3rs 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.

Original languageEnglish (US)
Article number44444
JournalScientific Reports
Volume7
DOIs
StatePublished - Mar 15 2017

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Receptor, Melanocortin, Type 3
Appointments and Schedules
Neurons
Meals
Appetite
Food
5' Untranslated Regions
Neuropeptide Y
Photoperiod
Fasting
Conditioning (Psychology)
Peptides

ASJC Scopus subject areas

  • General

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Melanocortin-3 receptors expressed in Nkx2.1(+ve) neurons are sufficient for controlling appetitive responses to hypocaloric conditioning. / Girardet, Clémence; Mavrikaki, Maria M.; Stevens, Joseph R.; Miller, Courtney A.; Marks, Daniel; Butler, Andrew A.

In: Scientific Reports, Vol. 7, 44444, 15.03.2017.

Research output: Contribution to journalArticle

Girardet, Clémence ; Mavrikaki, Maria M. ; Stevens, Joseph R. ; Miller, Courtney A. ; Marks, Daniel ; Butler, Andrew A. / Melanocortin-3 receptors expressed in Nkx2.1(+ve) neurons are sufficient for controlling appetitive responses to hypocaloric conditioning. In: Scientific Reports. 2017 ; Vol. 7.
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