A neurogenic signature involving monoamine oxidase-a controls human thermogenic adipose tissue development
- University of Massachusetts Medical School, United States
Abstract
Mechanisms that control 'beige/brite' thermogenic adipose tissue development may be harnessed to improve human metabolic health. To define these mechanisms, we developed a species-hybrid model in which human mesenchymal progenitor cells were used to develop white or thermogenic/beige adipose tissue in mice. The hybrid adipose tissue developed distinctive features of human adipose tissue, such as larger adipocyte size, despite its neurovascular architecture being entirely of murine origin. Thermogenic adipose tissue recruited a denser, qualitatively distinct vascular network, differing in genes mapping to circadian rhythm pathways, and denser sympathetic innervation. The enhanced thermogenic neurovascular network was associated with human adipocyte expression of THBS4, TNC, NTRK3 and SPARCL1, which enhance neurogenesis, and decreased expression of MAOA and ACHE, which control neurotransmitter tone. Systemic inhibition of MAOA, which is present in human but absent in mouse adipocytes, induced browning of human but not mouse adipose tissue, revealing the physiological relevance of this pathway. Our results reveal species-specific cell type dependencies controlling the development of thermogenic adipose tissue and point to human adipocyte MAOA as a potential target for metabolic disease therapy.
Data availability
RNASeq data has been deposited in the Gene Expression Omnibus under the accession number GSE200141.
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A neurogenic signature involving monoamine oxidase-a controls human thermogenic adipose tissue developmentNCBI Gene Expression Omnibus, GSE200141.
Article and author information
Author details
Zinger Yang Loureiro
Funding
National Institutes of Health (DK089101)
- Silvia Corvera
National Institutes of Health (DK123028)
- Silvia Corvera
National Institutes of Health (GM135751)
- Javier Solivan-Rivera
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Joel K Elmquist, University of Texas Southwestern Medical Center, United States
Ethics
Animal experimentation: All procedures were performed in accordance with the University of Massachusetts Medical School's Institutional Animal Care and use Committee protocol PROTO202100015.
Version history
- Preprint posted: December 30, 2021 (view preprint)
- Received: March 25, 2022
- Accepted: September 9, 2022
- Accepted Manuscript published: September 15, 2022 (version 1)
- Accepted Manuscript updated: September 20, 2022 (version 2)
- Version of Record published: September 28, 2022 (version 3)
- Version of Record updated: September 30, 2022 (version 4)
Copyright
© 2022, Solivan-Rivera 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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A neurogenic signature involving monoamine oxidase-a controls human thermogenic adipose tissue development
eLife 11:e78945.
https://doi.org/10.7554/eLife.78945
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