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

  1. Anthony H Tsang

    Institute of Neurobiology, University of Lübeck, Lübeck, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Christiane E Koch

    Institute of Neurobiology, University of Lübeck, Lübeck, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Jana-Thabea Kiehn

    Institute of Neurobiology, University of Lübeck, Lübeck, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Cosima X Schmidt

    Institute of Neurobiology, University of Lübeck, Lübeck, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Henrik Oster

    Institute of Neurobiology, University of Lübeck, Lübeck, Germany
    For correspondence
    henrik.oster@uni-luebeck.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1414-7068

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.

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).

Reviewing Editor

  1. Amita Sehgal, Howard Hughes Medical Institute, University of Pennsylvania, United States

Publication history

  1. Received: January 23, 2020
  2. Accepted: July 8, 2020
  3. Accepted Manuscript published: July 9, 2020 (version 1)
  4. Version of Record published: July 22, 2020 (version 2)

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.

Metrics

  • 1,295
    Page views
  • 248
    Downloads
  • 7
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Anthony H Tsang
  2. Christiane E Koch
  3. Jana-Thabea Kiehn
  4. Cosima X Schmidt
  5. Henrik Oster
(2020)
An adipokine feedback regulating diurnal food intake rhythms in mice
eLife 9:e55388.
https://doi.org/10.7554/eLife.55388

Further reading

    1. Computational and Systems Biology
    2. Genetics and Genomics
    Noushin Hadadi et al.
    Tools and Resources

    Thermal adaptation is an extensively used intervention for enhancing or suppressing thermogenic and mitochondrial activity in adipose tissues. As such, it has been suggested as a potential lifestyle intervention for body weight maintenance. While the metabolic consequences of thermal acclimation are not limited to the adipose tissues, the impact on the rest of the tissues in context of their gene expression profile remains unclear. Here, we provide a systematic characterization of the effects in a comparative multi-tissue RNA sequencing approach following exposure of mice to 10 °C, 22 °C, or 34 °C in a panel of organs consisting of spleen, bone marrow, spinal cord, brain, hypothalamus, ileum, liver, quadriceps, subcutaneous-, visceral- and brown adipose tissues. We highlight that transcriptional responses to temperature alterations exhibit a high degree of tissue-specificity both at the gene level and at GO enrichment gene sets, and show that the tissue-specificity is not directed by the distinct basic gene expression pattern exhibited by the various organs. Our study places the adaptation of individual tissues to different temperatures in a whole-organism framework and provides integrative transcriptional analysis necessary for understanding the temperature-mediated biological programming.

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics
    Bethany Sump et al.
    Research Article

    For some inducible genes, the rate and molecular mechanism of transcriptional activation depends on the prior experiences of the cell. This phenomenon, called epigenetic transcriptional memory, accelerates reactivation and requires both changes in chromatin structure and recruitment of poised RNA Polymerase II (RNAPII) to the promoter. Memory of inositol starvation in budding yeast involves a positive feedback loop between transcription factor-dependent interaction with the nuclear pore complex and histone H3 lysine 4 dimethylation (H3K4me2). While H3K4me2 is essential for recruitment of RNAPII and faster reactivation, RNAPII is not required for H3K4me2. Unlike RNAPII-dependent H3K4me2 associated with transcription, RNAPII-independent H3K4me2 requires Nup100, SET3C, the Leo1 subunit of the Paf1 complex and, upon degradation of an essential transcription factor, is inherited through multiple cell cycles. The writer of this mark (COMPASS) physically interacts with the potential reader (SET3C), suggesting a molecular mechanism for the spreading and re-incorporation of H3K4me2 following DNA replication.