Brown and beige adipose tissue regulate systemic metabolism through a metabolite interorgan signaling axis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-03-26

AUTHORS

Anna Whitehead, Fynn N. Krause, Amy Moran, Amanda D. V. MacCannell, Jason L. Scragg, Ben D. McNally, Edward Boateng, Steven A. Murfitt, Samuel Virtue, John Wright, Jack Garnham, Graeme R. Davies, James Dodgson, Jurgen E. Schneider, Andrew J. Murray, Christopher Church, Antonio Vidal-Puig, Klaus K. Witte, Julian L. Griffin, Lee D. Roberts

ABSTRACT

Brown and beige adipose tissue are emerging as distinct endocrine organs. These tissues are functionally associated with skeletal muscle, adipose tissue metabolism and systemic energy expenditure, suggesting an interorgan signaling network. Using metabolomics, we identify 3-methyl-2-oxovaleric acid, 5-oxoproline, and β-hydroxyisobutyric acid as small molecule metabokines synthesized in browning adipocytes and secreted via monocarboxylate transporters. 3-methyl-2-oxovaleric acid, 5-oxoproline and β-hydroxyisobutyric acid induce a brown adipocyte-specific phenotype in white adipocytes and mitochondrial oxidative energy metabolism in skeletal myocytes both in vitro and in vivo. 3-methyl-2-oxovaleric acid and 5-oxoproline signal through cAMP-PKA-p38 MAPK and β-hydroxyisobutyric acid via mTOR. In humans, plasma and adipose tissue 3-methyl-2-oxovaleric acid, 5-oxoproline and β-hydroxyisobutyric acid concentrations correlate with markers of adipose browning and inversely associate with body mass index. These metabolites reduce adiposity, increase energy expenditure and improve glucose and insulin homeostasis in mouse models of obesity and diabetes. Our findings identify beige adipose-brown adipose-muscle physiological metabokine crosstalk. More... »

PAGES

1905

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-021-22272-3

    DOI

    http://dx.doi.org/10.1038/s41467-021-22272-3

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1136687090

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/33772024


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