The p75 neurotrophin receptor in AgRP neurons is necessary for homeostatic feeding and food anticipation
Abstract
Networks of neurons control feeding and activity patterns by integrating internal metabolic signals of energy balance with external environmental cues such as time-of-day. Proper circadian alignment of feeding behavior is necessary to prevent metabolic disease, and thus it is imperative that molecular players that maintain neuronal coordination of energy homeostasis are identified. Here, we demonstrate that mice lacking the p75 neurotrophin receptor, p75NTR, decrease their feeding and food anticipatory behavior (FAA) in response to daytime, but not nighttime, restricted feeding. These effects lead to increased weight loss, but do not require p75NTR during development. Instead, p75NTR is required for fasting-induced activation of neurons within the arcuate hypothalamus. Indeed, p75NTR specifically in AgRP neurons is required for FAA in response to daytime restricted feeding. These findings establish p75NTR as a novel regulator gating behavioral response to food scarcity and time-of-day dependence of circadian food anticipation.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Hartwell Foundation
- Christopher D Deppmann
National Institutes of Health (T32-GM7267-39)
- Brandon Podyma
National Institutes of Health (T32-GM7055-45)
- Brandon Podyma
National Institutes of Health (R01-GM121937)
- Ali Deniz Güler
National Institutes of Health (RO1-AG055059)
- Sung Ok Yoon
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#3795, 3975, 4183, 4191, 4200) of the University of Virginia.
Copyright
© 2020, Podyma et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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