Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
4-Methylumbelliferone improves the thermogenic capacity of brown adipose tissue
Show others and affiliations
Number of Authors: 252019 (English)In: Nature Metabolism, E-ISSN 2522-5812, Vol. 1, no 5, p. 546-559Article in journal (Refereed) Published
Abstract [en]

Therapeutic increase in brown adipose tissue (BAT) thermogenesis is of great interest, as BAT activation counteracts obesity and insulin resistance. Hyaluronan (HA) is a glycosaminoglycan, found in the extracellular matrix, that is synthesized by HA synthases (HAS1, HAS2, and HAS3) from sugar precursors and accumulates in diabetic conditions. Its synthesis can be inhibited by the small molecule 4-methylumbelliferone (4-MU). Here we show that inhibition of HA synthesis by 4-MU or genetic deletion of Has2 and Has3 improves the thermogenic capacity of BAT, reduces body-weight gain, and improves glucose homeostasis independently of adrenergic stimulation in mice on a diabetogenic diet. In this context, we validated a novel magnetic resonce T2 mapping approach for in vivo visualization of BAT activation. Inhibition of HA synthesis increases glycolysis, BAT respiration, and uncoupling protein 1 (UCP1) expression. In addition, we show that 4-MU increases BAT capacity without inducing chronic stimulation and propose that 4-MU, a clinically approved, prescription-free drug, could be repurposed to treat obesity and diabetes.

Place, publisher, year, edition, pages
2019. Vol. 1, no 5, p. 546-559
National Category
Cell and Molecular Biology Biochemistry and Molecular Biology Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:su:diva-177816DOI: 10.1038/s42255-019-0055-6ISI: 000500742000009PubMedID: 31602424OAI: oai:DiVA.org:su-177816DiVA, id: diva2:1384027
Available from: 2020-01-09 Created: 2020-01-09 Last updated: 2020-01-09Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Sunkari, Vivekananda G.Keipert, SusanneJastroch, Martin
By organisation
Department of Molecular Biosciences, The Wenner-Gren Institute
Cell and Molecular BiologyBiochemistry and Molecular BiologyEndocrinology and Diabetes

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 6 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf