1. Genetics and Genomics
  2. Neuroscience

An adipokine feedback regulating diurnal food intake rhythms in mice

  1. Anthony H Tsang
  2. Christiane E Koch
  3. Jana-Thabea Kiehn
  4. Cosima X Schmidt
  5. Henrik Oster  Is a corresponding author
  1. University of Lübeck, Germany
https://doi.org/10.7554/eLife.55388
Share this article
Cite this article
  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
  2. Download BibTeX
  3. Download .RIS

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).

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

  • 1,780
    views
  • 330
    downloads
  • 25
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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

Share this article

https://doi.org/10.7554/eLife.55388

Categories and tags

Research organism

Further reading

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Deep sequencing of yeast and mouse tRNAs and tRNA fragments using OTTR

    Hans Tobias Gustafsson, Lucas Ferguson ... Oliver J Rando
    Research Article

    Among the major classes of RNAs in the cell, tRNAs remain the most difficult to characterize via deep sequencing approaches, as tRNA structure and nucleotide modifications can each interfere with cDNA synthesis by commonly-used reverse transcriptases (RTs). Here, we benchmark a recently-developed RNA cloning protocol, termed Ordered Two-Template Relay (OTTR), to characterize intact tRNAs and tRNA fragments in budding yeast and in mouse tissues. We show that OTTR successfully captures both full-length tRNAs and tRNA fragments in budding yeast and in mouse reproductive tissues without any prior enzymatic treatment, and that tRNA cloning efficiency can be further enhanced via AlkB-mediated demethylation of modified nucleotides. As with other recent tRNA cloning protocols, we find that a subset of nucleotide modifications leave misincorporation signatures in OTTR datasets, enabling their detection without any additional protocol steps. Focusing on tRNA cleavage products, we compare OTTR with several standard small RNA-Seq protocols, finding that OTTR provides the most accurate picture of tRNA fragment levels by comparison to "ground truth" Northern blots. Applying this protocol to mature mouse spermatozoa, our data dramatically alter our understanding of the small RNA cargo of mature mammalian sperm, revealing a far more complex population of tRNA fragments - including both 5′ and 3′ tRNA halves derived from the majority of tRNAs – than previously appreciated. Taken together, our data confirm the superior performance of OTTR to commercial protocols in analysis of tRNA fragments, and force a reappraisal of potential epigenetic functions of the sperm small RNA payload.

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Major nuclear locales define nuclear genome organization and function beyond A and B compartments

    Omid Gholamalamdari, Tom van Schaik ... Andrew S Belmont
    Research Article

    Models of nuclear genome organization often propose a binary division into active versus inactive compartments yet typically overlook nuclear bodies. Here, we integrated analysis of sequencing and image-based data to compare genome organization in four human cell types relative to three different nuclear locales: the nuclear lamina, nuclear speckles, and nucleoli. Although gene expression correlates mostly with nuclear speckle proximity, DNA replication timing correlates with proximity to multiple nuclear locales. Speckle attachment regions emerge as DNA replication initiation zones whose replication timing and gene composition vary with their attachment frequency. Most facultative LADs retain a partially repressed state as iLADs, despite their positioning in the nuclear interior. Knock out of two lamina proteins, Lamin A and LBR, causes a shift of H3K9me3-enriched LADs from lamina to nucleolus, and a reciprocal relocation of H3K27me3-enriched partially repressed iLADs from nucleolus to lamina. Thus, these partially repressed iLADs appear to compete with LADs for nuclear lamina attachment with consequences for replication timing. The nuclear organization in adherent cells is polarized with nuclear bodies and genomic regions segregating both radially and relative to the equatorial plane. Together, our results underscore the importance of considering genome organization relative to nuclear locales for a more complete understanding of the spatial and functional organization of the human genome.