Journal Article

IL-25–induced shifts in macrophage polarization promote development of beige fat and improve metabolic homeostasis in mice

Zhang, Hui, Luo, Shiya, Gong, Baoyong, Ma, Lei, Gao, Guoquan, Yang, Zhonghan, Li, Lingyi, Yang, Xia, Qi, Weiwei, Feng, Juan, Li, Jin, Zhou, Ti, Zhao, Zewei

2021

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adipocytes / Adipocytes, Beige - physiology / Adipose tissue / Adipose Tissue, Beige - growth & development / Adrenergic beta-3 Receptor Agonists / Adrenergic receptors / Animals / Biology and Life Sciences / Biosynthesis / Bisphosphonates / Catecholamine / Catecholamines / Cell activation / Clodronic acid / Cold / Cold Temperature / Cytokines / Depletion / Fat / Gene expression / High fat diet / Homeostasis / Hydroxylase / Innervation / Insulin Resistance / Interleukin 13 / Interleukin 17 / Interleukin 4 / Interleukin-4 - metabolism / Interleukins / Interleukins - metabolism / Macrophages / Macrophages - physiology / Male / Medicine and Health Sciences / Metabolic disorders / Metabolism / Mice / Mice, Inbred C57BL / Norepinephrine / Obesity / Obesity - metabolism / Physiological aspects / Physiological research / Proteins / Receptors / Research and Analysis Methods / Signaling / Thermogenesis / Tyrosine / Tyrosine 3-monooxygenase / Uncoupling protein 1 / Uncoupling Protein 1 - physiology