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.
Highlights
Neuronal circuits originating in the hypothalamus direct behavioral responses to match an organism’s perception of scarce or excess energy environments (Morton et al, 2006)
To establish whether p75NTR is involved in any gross processes of energy homeostasis, we first examined body weight, food intake, and locomotor activity in ad libitum fed mice harboring germline knockout alleles of p75NTR (Ngfr-KO) (Lee et al, 1992)
These data suggest that p75NTR does not influence energy homeostasis under ad libitum conditions
Summary
Neuronal circuits originating in the hypothalamus direct behavioral responses to match an organism’s perception of scarce or excess energy environments (Morton et al, 2006). Scarcity due to a limited window of food availability (e.g. a prey species emerges to forage for only a few hours) is capable of inducing adaptation of this ostensibly circadian feeding circuit. The context of this timing information is so significant that regularly recurring cycles of food availability can lead organisms to modify their behavior and physiology, changing their locomotor activity, glucocorticoid levels, and body temperature to better match the predicted time of food availability (Patton and Mistlberger, 2013). A growing body of evidence suggests that desynchronization of feeding relative to the normal circadian time of eating adversely impacts metabolic health (Challet, 2019; Hatori et al, 2012; Pan et al, 2011; Sutton et al, 2018)
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