Title :

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

Author(s) :

Yang, J. [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
de Vries, H.D. [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Mayeuf-Louchart, Alicia [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Stroeve, J.H. [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Bloks, V.W. [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Koehorst, M. [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Duez, H. [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Staels, B. [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Kuipers, F. [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
van Zutphen, T. [Auteur]
University Medical Center Groningen [Groningen] [UMCG]

Journal title :

Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids

Pages :

159257

Publisher :

Elsevier

Publication date :

2023

ISSN :

1388-1981

English keyword(s) :

Brown adipose tissue
FXR
Extracellular matrix
Cold exposure
β3-Adrenergic receptor agonist
Bile acids

HAL domain(s) :

Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Endocrinologie et métabolisme
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Génomique, Transcriptomique et Protéomique [q-bio.GN]

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (RNMCD) - U1011

Source :

Harvested from HAL