β-Klotho deficiency protects against obesity through a crosstalk between liver, microbiota, and brown adipose tissue.

Détails

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Etat: Public
Version: de l'auteur
Licence: Non spécifiée
ID Serval
serval:BIB_94A6C8A6A9EA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
β-Klotho deficiency protects against obesity through a crosstalk between liver, microbiota, and brown adipose tissue.
Périodique
JCI insight
Auteur(s)
Somm E., Henry H., Bruce S.J., Aeby S., Rosikiewicz M., Sykiotis G.P., Asrih M., Jornayvaz F.R., Denechaud P.D., Albrecht U., Mohammadi M., Dwyer A., Acierno J.S., Schoonjans K., Fajas L., Greub G., Pitteloud N.
ISSN
2379-3708 (Electronic)
ISSN-L
2379-3708
Statut éditorial
Publié
Date de publication
20/04/2017
Peer-reviewed
Oui
Volume
2
Numéro
8
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
β-Klotho (encoded by Klb) is the obligate coreceptor mediating FGF21 and FGF15/19 signaling. Klb-/- mice are refractory to beneficial action of pharmacological FGF21 treatment including stimulation of glucose utilization and thermogenesis. Here, we investigated the energy homeostasis in Klb-/- mice on high-fat diet in order to better understand the consequences of abrogating both endogenous FGF15/19 and FGF21 signaling during caloric overload. Surprisingly, Klb-/- mice are resistant to diet-induced obesity (DIO) owing to enhanced energy expenditure and BAT activity. Klb-/- mice exhibited not only an increase but also a shift in bile acid (BA) composition featured by activation of the classical (neutral) BA synthesis pathway at the expense of the alternative (acidic) pathway. High hepatic production of cholic acid (CA) results in a large excess of microbiota-derived deoxycholic acid (DCA). DCA is specifically responsible for activating the TGR5 receptor that stimulates BAT thermogenic activity. In fact, combined gene deletion of Klb and Tgr5 or antibiotic treatment abrogating bacterial conversion of CA into DCA both abolish DIO resistance in Klb-/- mice. These results suggested that DIO resistance in Klb-/- mice is caused by high levels of DCA, signaling through the TGR5 receptor. These data also demonstrated that gut microbiota can regulate host thermogenesis via conversion of primary into secondary BA. Pharmacologic or nutritional approaches to selectively modulate BA composition may be a promising target for treating metabolic disorders.
Mots-clé
Endocrinology, Metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
05/07/2019 15:11
Dernière modification de la notice
24/08/2019 6:09
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