Leptin-receptor neurons in the dorsomedial hypothalamus regulate diurnal patterns of feeding, locomotion, and metabolism
- University of Washington, United States
- Barrow Neurological Institute, United States
Abstract
Animal behavior and metabolism are tightly coordinated with sleep-wake cycles governed by the brain in harmony with environmental light:dark cycles. Within the brain, the dorsomedial hypothalamic nucleus (DMH) has been implicated in the integrative control of feeding, energy homeostasis, and circadian rhythms,1 but the underlying cell types are unknown. Here, we identify a role for DMH leptin receptor-expressing neurons (DMHLepR) in this integrative control. Using a viral approach, we show that silencing neurotransmission in DMHLepR neurons in adult mice not only increases body weight and adiposity, but also phase-advances diurnal rhythms of feeding and metabolism into the light-cycle and abolishes the normal increase in dark-cycle locomotor activity (LMA) characteristic of nocturnal rodents. Finally, DMHLepR-silenced mice fail to entrain to a restrictive change in food availability. Together, these findings identify DMHLepR neurons as critical determinants of the daily time of feeding and associated metabolic rhythms.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1-4.
Article and author information
Author details
Michael W Schwartz
Funding
National Institutes of Health (F31-DK113673)
- Chelsea L Faber
American Diabetes Association (ADA 1-19-PDF-103)
- Jennifer D Deem
U.S. Department of Defense (W81XWH2010250)
- Zaman Mirzadeh
National Institutes of Health (DK128802)
- Zaman Mirzadeh
National Institutes of Health (T32-GM095421)
- Chelsea L Faber
National Institutes of Health (DK089056)
- Gregory J Morton
National Institutes of Health (DK124238)
- Gregory J Morton
National Institutes of Health (DK083042)
- Michael W Schwartz
National Institutes of Health (DK101997)
- Michael W Schwartz
National Institutes of Health (T32 DK007247)
- Chelsea L Faber
National Institutes of Health (T32 HL007028)
- Jennifer D Deem
American Diabetes Association (ADA 1-19-IBS-192)
- Gregory J Morton
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Animal Care Committee at the University of Washington. (Jackson Laboratory no. 008320)
Copyright
© 2021, Faber 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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Leptin-receptor neurons in the dorsomedial hypothalamus regulate diurnal patterns of feeding, locomotion, and metabolism
eLife 10:e63671.
https://doi.org/10.7554/eLife.63671
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