IL-25-induced shifts in macrophage polarization promote development of beige fat and improve metabolic homeostasis in mice.
PLoS Biol
; 19(8): e3001348, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-34351905
ABSTRACT
Beige fat dissipates energy and functions as a defense against cold and obesity, but the mechanism for its development is unclear. We found that interleukin (IL)-25 signaling through its cognate receptor, IL-17 receptor B (IL-17RB), increased in adipose tissue after cold exposure and ß3-adrenoceptor agonist stimulation. IL-25 induced beige fat formation in white adipose tissue (WAT) by releasing IL-4 and IL-13 and promoting alternative activation of macrophages that regulate innervation and up-regulate tyrosine hydroxylase (TH) up-regulation to produce more catecholamine including norepinephrine (NE). Blockade of IL-4Rα or depletion of macrophages with clodronate-loaded liposomes in vivo significantly impaired the beige fat formation in WAT. Mice fed with a high-fat diet (HFD) were protected from obesity and related metabolic disorders when given IL-25 through a process that involved the uncoupling protein 1 (UCP1)-mediated thermogenesis. In conclusion, the activation of IL-25 signaling in WAT may have therapeutic potential for controlling obesity and its associated metabolic disorders.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Interleucinas
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Tecido Adiposo Bege
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Adipócitos Bege
/
Macrófagos
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article