Enhanced C/EBPβ function promotes hypertrophic versus hyperplastic fat tissue growth and prevents steatosis in response to high-fat diet feeding

  1. Christine Müller
  2. Laura M Zidek
  3. Sabrina Eichwald
  4. Gertrud Kortman
  5. Mirjam H Koster
  6. Cornelis F Calkhoven  Is a corresponding author
  1. University Medical Center Groningen, Netherlands
  2. Leibniz Institute on Aging - Fritz Lipmann Institute, Germany

Abstract

Chronic obesity is correlated with severe metabolic and cardiovascular diseases as well as with an increased risk for developing cancers. Obesity is usually characterized by fat accumulation in enlarged - hypertrophic – adipocytes that are a source of inflammatory mediators, which promote the development and progression of metabolic disorders. Yet, in certain healthy obese individuals, fat is stored in metabolically more favorable hyperplastic fat tissue that contains an increased number of smaller adipocytes that are less inflamed. In a previous study we demonstrated that loss of the inhibitory protein-isoform C/EBPβ-LIP and the resulting augmented function of the transactivating isoform C/EBPβ-LAP promotes fat metabolism under normal feeding conditions and expands health- and lifespan in mice. Here we show that in mice on a high-fat diet, LIP-deficiency results in adipocyte hyperplasia associated with reduced inflammation and metabolic improvements. Furthermore, fat storage in subcutaneous depots is significantly enhanced specifically in LIP-deficient male mice. Our data identify C/EBPβ as a regulator of adipocyte fate in response to increased fat intake, which has major implications for metabolic health and aging.

Data availability

Source data are included in the Source Data files

Article and author information

Author details

  1. Christine Müller

    European Research Institute for the Biology of Ageing, University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1974-4053
  2. Laura M Zidek

    Leibniz Institute on Aging - Fritz Lipmann Institute, Jena, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Sabrina Eichwald

    Leibniz Institute on Aging - Fritz Lipmann Institute, Jena, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Gertrud Kortman

    European Research Institute for the Biology of Ageing, University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Mirjam H Koster

    Department of Pediatrics, University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Cornelis F Calkhoven

    European Research Institute for the Biology of Ageing, University Medical Center Groningen, Groningen, Netherlands
    For correspondence
    c.f.calkhoven@umcg.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6318-7210

Funding

Deutsche Forschungsgemeinschaft (CA 283/1-1)

  • Laura M Zidek

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Matt Kaeberlein, University of Washington, United States

Ethics

Animal experimentation: All animal experiments were performed in compliance with protocols approved by the Institutional Animal Care and Use committee (IACUC) of the Thüringer Landesamt für Verbraucherschutz (#03-005/13).

Version history

  1. Received: September 1, 2020
  2. Preprint posted: September 3, 2020 (view preprint)
  3. Accepted: April 8, 2022
  4. Accepted Manuscript published: April 22, 2022 (version 1)
  5. Version of Record published: May 5, 2022 (version 2)
  6. Version of Record updated: May 12, 2022 (version 3)

Copyright

© 2022, Müller 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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  1. Christine Müller
  2. Laura M Zidek
  3. Sabrina Eichwald
  4. Gertrud Kortman
  5. Mirjam H Koster
  6. Cornelis F Calkhoven
(2022)
Enhanced C/EBPβ function promotes hypertrophic versus hyperplastic fat tissue growth and prevents steatosis in response to high-fat diet feeding
eLife 11:e62625.
https://doi.org/10.7554/eLife.62625

Share this article

https://doi.org/10.7554/eLife.62625

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