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Grandoch, M.* ; Flögel, U.* ; Virtue, S.* ; Maier, J.K.* ; Jelenik, T.* ; Kohlmorgen, C.* ; Feldmann, K.* ; Ostendorf, Y.* ; Castañeda, T.R.* ; Zhou, Z.* ; Yamaguchi, Y.* ; Nascimento, E.B.M.* ; Sunkari, V.G.* ; Goy, C.* ; Kinzig, M.* ; Sörgel, F.* ; Bollyky, P.L.* ; Schrauwen, P.* ; Al-Hasani, H.* ; Roden, M.* ; Keipert, S. ; Vidal-Puig, A.* ; Jastroch, M. ; Haendeler, J.* ; Fischer, J.W.*

4-Methylumbelliferone improves the thermogenic capacity of brown adipose tissue.

Nat. Metab. 1, 546-559 (2019)
Postprint DOI PMC
Open Access Green
Therapeutic increase of 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, which is synthesized by HA synthases (Has1/Has2/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 the inhibition of HA-synthesis by 4-MU or genetic deletion of Has2/Has3 improves BAT`s thermogenic capacity, reduces body weight gain, and improves glucose homeostasis independently from adrenergic stimulation in mice on diabetogenic diet, as shown by a magnetic resonance T2 mapping approach. Inhibition of HA synthesis increases glycolysis, BAT respiration and uncoupling protein 1 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 2522-5812
e-ISSN 2522-5812
Zeitschrift Nature metabolism
Quellenangaben Band: 1, Heft: 5, Seiten: 546-559 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)