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4-Methylumbellifero...
4-Methylumbelliferone improves the thermogenic capacity of brown adipose tissue
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Grandoch, Maria (author)
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Floegel, Ulrich (author)
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Virtue, Sam (author)
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Maier, Julia K. (author)
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Jelenik, Tomas (author)
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Kohlmorgen, Christina (author)
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Feldmann, Kathrin (author)
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Ostendorf, Yanina (author)
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Castaneda, Tamara R. (author)
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Zhou, Zhou (author)
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Yamaguchi, Yu (author)
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Nascimento, Emmani B. M. (author)
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Sunkari, Vivekananda G. (author)
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Goy, Christine (author)
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Kinzig, Martina (author)
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Soergel, Fritz (author)
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Bollyky, Paul L. (author)
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Schrauwen, Patrick (author)
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Al-Hasani, Hadi (author)
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Roden, Michael (author)
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- Keipert, Susanne (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,German Center for Diabetes Research (DZD), Germany; Helmholtz Zentrum München, Germany
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Vidal-Puig, Antonio (author)
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- Jastroch, Martin (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,German Center for Diabetes Research (DZD), Germany; Helmholtz Zentrum München, Germany
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Haendeler, Judith (author)
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Fischer, Jens W. (author)
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(creator_code:org_t)
- 2019-04-22
- 2019
- English.
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In: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 1:5, s. 546-559
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Grandoch, Maria
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Floegel, Ulrich
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Virtue, Sam
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Maier, Julia K.
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Jelenik, Tomas
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Kohlmorgen, Chri ...
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show more...
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Feldmann, Kathri ...
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Ostendorf, Yanin ...
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Castaneda, Tamar ...
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Zhou, Zhou
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Yamaguchi, Yu
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Nascimento, Emma ...
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Sunkari, Vivekan ...
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Goy, Christine
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Kinzig, Martina
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Soergel, Fritz
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Bollyky, Paul L.
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Schrauwen, Patri ...
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Al-Hasani, Hadi
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Roden, Michael
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Keipert, Susanne
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Vidal-Puig, Anto ...
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Jastroch, Martin
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Haendeler, Judit ...
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Fischer, Jens W.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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Nature Metabolis ...
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Stockholm University