An adipokine feedback regulating diurnal food intake rhythms in mice
Abstract
Endogenous circadian clocks have evolved to anticipate 24-hour rhythms in environmental demands. Recent studies suggest that circadian rhythm disruption is a major risk factor for the development of metabolic disorders in humans. Conversely, alterations in energy state can disrupt circadian rhythms of behavior and physiology, creating a vicious circle of metabolic dysfunction. How peripheral energy state affects diurnal food intake, however, is still poorly understood. We here show that the adipokine adiponectin (ADIPOQ) regulates diurnal feeding rhythms through clocks in energy regulatory centers of the mediobasal hypothalamus (MBH). Adipoq-deficient mice show increased rest phase food intake associated with disrupted transcript rhythms of clock and appetite-regulating genes in the MBH. ADIPOQ regulates MBH clocks via AdipoR1-mediated upregulation of the core clock gene Bmal1. BMAL1, in turn, controls expression of orexigenic neuropeptide expression in the MBH. Together, these data reveal a systemic metabolic circuit to regulate central circadian clocks and energy intake.
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 to 8.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (GRK-1957)
- Henrik Oster
Deutsche Forschungsgemeinschaft (OS353-7/1)
- Henrik Oster
Volkswagen Foundation (Lichtenberg Professorship)
- Henrik Oster
Deutsche Forschungsgemeinschaft (OS353-10/1)
- Henrik Oster
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Amita Sehgal, Howard Hughes Medical Institute, University of Pennsylvania, United States
Ethics
Animal experimentation: All animal experiments were done after ethical assessment by the institutional animal welfare committee and licensed by the Office of Consumer Protection and Food Safety of the State of Lower Saxony (33.12.42502-04-12/0893, 33.14-42502-04-11/0604 and 33.9-42502-04-12/0748) or the Ministry of Agriculture of the State of Schleswig-Holstein (V 242-7224.122-4 (132-10/13)) in accordance with the German Law of Animal Welfare (TierSchG).
Version history
- Received: January 23, 2020
- Accepted: July 8, 2020
- Accepted Manuscript published: July 9, 2020 (version 1)
- Version of Record published: July 22, 2020 (version 2)
- Version of Record updated: December 14, 2022 (version 3)
Copyright
© 2020, Tsang 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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