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Inhibition of Meval...
Inhibition of Mevalonate Pathway Prevents Adipocyte Browning in Mice and Men by Affecting Protein Prenylation
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Balaz, M. (author)
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Becker, A. S. (author)
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Balazova, L. (author)
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Straub, L. (author)
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Muller, J. (author)
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Gashi, G. (author)
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Maushart, C. I. (author)
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Sun, W. F. (author)
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Dong, H. (author)
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Moser, C. (author)
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Horvath, C. (author)
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Efthymiou, V. (author)
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Rachamin, Y. (author)
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Modica, S. (author)
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Zellweger, C. (author)
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Bacanovic, S. (author)
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Stefanicka, P. (author)
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Varga, L. (author)
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Ukropcova, B. (author)
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Profant, M. (author)
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Opitz, L. (author)
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Amri, E. Z. (author)
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- Akula, Murali K (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Bergö, Martin, 1970 (author)
- Karolinska Institutet,Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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Ukropec, J. (author)
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Falk, C. (author)
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Zamboni, N. (author)
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Betz, M. J. (author)
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Burger, I. A. (author)
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Wolfrum, C. (author)
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(creator_code:org_t)
- Elsevier BV, 2019
- 2019
- English.
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In: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 29:4
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https://gup.ub.gu.se...
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Abstract
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- Recent research focusing on brown adipose tissue (BAT) function emphasizes its importance in systemic metabolic homeostasis. We show here that genetic and pharmacological inhibition of the mevalonate pathway leads to reduced human and mouse brown adipocyte function in vitro and impaired adipose tissue browning in vivo. A retrospective analysis of a large patient cohort suggests an inverse correlation between statin use and active BAT in humans, while we show in a prospective clinical trial that fluvastatin reduces thermogenic gene expression in human BAT. We identify geranylgeranyl pyrophosphate as the key mevalonate pathway intermediate driving adipocyte browning in vitro and in vivo, whose effects are mediated by geranylgeranyltransferases (GGTases), enzymes catalyzing geranylgeranylation of small GTP-binding proteins, thereby regulating YAP1/TAZ signaling through F-actin modulation. Conversely, adipocyte-specific ablation of GGTase I leads to impaired adipocyte browning, reduced energy expenditure, and glucose intolerance under obesogenic conditions, highlighting the importance of this pathway in modulating brown adipocyte functionality and systemic metabolism.
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)
Keyword
- adipose-tissue
- energy-expenditure
- glucose-uptake
- oxidative-metabolism
- insulin sensitivity
- statins
- differentiation
- thermogenesis
- expression
- farnesol
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Balaz, M.
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Becker, A. S.
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Balazova, L.
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Straub, L.
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Muller, J.
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Gashi, G.
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show more...
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Maushart, C. I.
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Sun, W. F.
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Dong, H.
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Moser, C.
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Horvath, C.
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Efthymiou, V.
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Rachamin, Y.
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Modica, S.
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Zellweger, C.
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Bacanovic, S.
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Stefanicka, P.
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Varga, L.
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Ukropcova, B.
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Profant, M.
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Opitz, L.
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Amri, E. Z.
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Akula, Murali K
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Bergö, Martin, 1 ...
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Ukropec, J.
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Falk, C.
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Zamboni, N.
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Betz, M. J.
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Burger, I. A.
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Wolfrum, C.
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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 ...
- Articles in the publication
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Cell Metabolism
- By the university
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University of Gothenburg
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Karolinska Institutet