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dc.contributor.authorWhitehead, Anna
dc.contributor.authorKrause, Fynn N.
dc.contributor.authorMoran, Amy
dc.contributor.authorMacCannell, Amanda D. V.
dc.contributor.authorScragg, Jason L.
dc.contributor.authorMcNally, Ben D.
dc.contributor.authorBoateng, Edward
dc.contributor.authorMurfitt, Steven A.
dc.contributor.authorVirtue, Samuel
dc.contributor.authorWright, John
dc.contributor.authorGarnham, Jack
dc.contributor.authorDavies, Graeme R.
dc.contributor.authorDodgson, James
dc.contributor.authorSchneider, Jurgen E.
dc.contributor.authorMurray, Andrew J.
dc.contributor.authorChurch, Christopher
dc.contributor.authorVidal-Puig, Antonio
dc.contributor.authorWitte, Klaus K.
dc.contributor.authorGriffin, Julian L.
dc.contributor.authorRoberts, Lee D.
dc.date.accessioned2021-03-26T16:21:13Z
dc.date.available2021-03-26T16:21:13Z
dc.date.issued2021-03-26
dc.date.submitted2020-06-26
dc.identifier.others41467-021-22272-3
dc.identifier.other22272
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/319247
dc.description.abstractAbstract: 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.
dc.languageen
dc.publisherNature Publishing Group UK
dc.subjectArticle
dc.subject/631/443/319/2723
dc.subject/631/443/319/1557
dc.subject/631/443/319/1642
dc.subject/631/443/319/320
dc.subject/38/89
dc.subject/38/90
dc.subject/38/91
dc.subject/38/77
dc.subject/38/1
dc.subject/38/39
dc.subject/38/43
dc.subject/59/78
dc.subject/64/60
dc.subject/82/51
dc.subject/82/58
dc.subject/96/63
dc.subject/96/106
dc.subject/13/109
dc.subject/14/19
dc.subjectarticle
dc.titleBrown and beige adipose tissue regulate systemic metabolism through a metabolite interorgan signaling axis
dc.typeArticle
dc.date.updated2021-03-26T16:21:12Z
prism.issueIdentifier1
prism.publicationNameNature Communications
prism.volume12
dc.identifier.doi10.17863/CAM.66367
dcterms.dateAccepted2021-03-05
rioxxterms.versionofrecord10.1038/s41467-021-22272-3
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidWhitehead, Anna [0000-0002-1213-4853]
dc.contributor.orcidKrause, Fynn N. [0000-0001-6664-2637]
dc.contributor.orcidMurray, Andrew J. [0000-0002-0929-9315]
dc.contributor.orcidVidal-Puig, Antonio [0000-0003-4220-9577]
dc.contributor.orcidWitte, Klaus K. [0000-0002-7146-7105]
dc.contributor.orcidRoberts, Lee D. [0000-0002-1455-5248]
dc.identifier.eissn2041-1723
pubs.funder-project-idDiabetes UK (16/0005382)
pubs.funder-project-idRCUK | Biotechnology and Biological Sciences Research Council (BBSRC) (BB/R013500/1)
pubs.funder-project-idRCUK | Medical Research Council (MRC) (MR/R014086/1)


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