Open AccessIL-25–induced shifts in macrophage polarization promote development of beige fat and improve metabolic homeostasis in mice
Author(s) -
Lingyi Li,
Lei Ma,
Zewei Zhao,
Shiya Luo,
Baoyong Gong,
Jin Li,
Juan Feng,
Hui Zhang,
Weiwei Qi,
Ti Zhou,
Xia Yang,
Guoquan Gao
Publication year - 2021
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3001348
Subject(s) - biology , endocrinology , thermogenesis , white adipose tissue , medicine , adipose tissue , receptor , agonist , macrophage polarization , energy homeostasis , homeostasis , signal transduction , brown adipose tissue , stimulation , microbiology and biotechnology , macrophage , obesity , biochemistry , in vitro
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 β3-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.