Role of bile acid receptor FXR in development and function of brown adipose tissue.

Autor: Yang J; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen 9700RB, the Netherlands., de Vries HD; Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen 9700RB, the Netherlands; Faculty Campus Fryslân, University of Groningen, Leeuwarden, the Netherlands., Mayeuf-Louchart A; Univ. Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1011-EGID, F-59000 Lille, France., Stroeve JH; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen 9700RB, the Netherlands., Bloks VW; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen 9700RB, the Netherlands., Koehorst M; Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen 9700RB, the Netherlands., Duez H; Univ. Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1011-EGID, F-59000 Lille, France., Staels B; Univ. Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1011-EGID, F-59000 Lille, France., Kuipers F; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen 9700RB, the Netherlands; European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: f.kuipers@umcg.nl., van Zutphen T; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen 9700RB, the Netherlands; Faculty Campus Fryslân, University of Groningen, Leeuwarden, the Netherlands. Electronic address: t.van.zutphen@umcg.nl.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular and cell biology of lipids [Biochim Biophys Acta Mol Cell Biol Lipids] 2023 Feb; Vol. 1868 (2), pp. 159257. Date of Electronic Publication: 2022 Nov 17.
DOI: 10.1016/j.bbalip.2022.159257
Abstrakt: Bile acids act as signalling molecules that contribute to maintenance of energy homeostasis in mice and humans. Activation of G-protein-coupled bile acid receptor TGR5 induces energy expenditure in brown adipose tissue (BAT). However, a role for the nuclear bile acid receptor Farnesoid X receptor (FXR) in BAT has remained ambiguous. We aimed to study the potential role of FXR in BAT development and functioning. Here we demonstrate low yet detectable expression of the α1/2 isoforms of FXR in murine BAT that markedly decreases upon cold exposure. Moderate adipose tissue-specific FXR overexpression in mice induces pronounced BAT whitening, presenting with large intracellular lipid droplets and extracellular collagen deposition. Expression of thermogenic marker genes including the target of Tgr5, Dio2, was significantly lower in BAT of chow-fed aP2-hFXR mice compared to wild-type controls. Transcriptomic analysis revealed marked up-regulation of extracellular matrix formation and down-regulation of mitochondrial functions in BAT from aP2-hFXR mice. In addition, markers of cell type lineages deriving from the dermomyotome, such as myocytes, as well as markers of cellular senescence were strongly induced. The response to cold and β3-adrenergic receptor agonism was blunted in these mice, yet resolved BAT whitening. Newborn cholestatic Cyp2c70 -/- mice with a human-like bile acid profile also showed distinct BAT whitening and upregulation of myocyte-specific genes, while thermogenic markers were down-regulated. Ucp1 expression inversely correlated with plasma bile acid levels. Therefore, bile acid signalling via FXR has a role in BAT function already early in tissue development. Functionally, FXR activation appears to oppose TGR5-mediated thermogenesis.
Competing Interests: Declaration of competing interest All authors have no conflict of interest.
(Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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