Enhanced C/EBPβ function promotes hypertrophic versus hyperplastic fat tissue growth and prevents steatosis in response to high-fat diet feeding
- University Medical Center Groningen, Netherlands
- 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.
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Source data are included in the Source Data files
Article and author information
Author details
Cornelis F Calkhoven
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.
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).
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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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
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