title: IL-33-driven ILC2/eosinophil axis in fat is induced by sympathetic tone and suppressed by obesity.
abstract: Group 2 innate lymphoid cells (ILC2s) in white adipose tissue (WAT) promote WAT browning and assist in preventing the development of obesity. However, how ILC2 in adipose tissue is regulated remains largely unknown. Here, our study shows that ILC2s are present in brown adipose tissue (BAT) as well as subcutaneous and epididymal WAT (sWAT and eWAT). The fractions of ILC2s, natural killer T (NKT) cells and eosinophils in sWAT, eWAT and BAT are significantly decreased by high-fat-diet (HFD) feeding and leptin deficiency-induced obesity. Consistent with this, the adipose expression and circulating levels of IL-33, a key inducing cytokine of ILC2, are significantly downregulated by obesity. Furthermore, administration of IL-33 markedly increases the fraction of ILC2 and eosinophil as well as the expression of UCP1 and tyrosine hydroxylase (TH), a rate-limiting enzyme in catecholamine biosynthesis, in adipose tissue of HFD-fed mice. On the other hand, cold exposure induces the expression levels of IL-33 and UCP1 and the population of ILC2 and eosinophil in sWAT, and these promoting effects of cold stress are reversed by neutralization of IL-33 signaling in vivo Moreover, the basal and cold-induced IL-33 and ILC2/eosinophil pathways are significantly suppressed by sympathetic denervation via local injection of 6-hydroxydopamine (6-OHDA) in sWAT. Taken together, our data suggest that the ILC2/eosinophil axis in adipose tissue is regulated by sympathetic nervous system and obesity in IL-33-dependent manner, and IL-33-driven ILC2/eosinophil axis is implicated in the development of obesity.
authors: Department of Biochemistry and Molecular BiologyUniversity of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of ChinaCollege of Life Science, Hunan Normal University, Changsha, Hunan, China.
authors: Xiaofeng
authors: X
authors: Ding
authors: Department of Biochemistry and Molecular BiologyUniversity of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA Department of Metabolism and EndocrinologyMetabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Yan
authors: Y
authors: Luo
authors: Department of Biochemistry and Molecular BiologyUniversity of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA Department of Molecular Genetics and MicrobiologyUniversity of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors: Xing
authors: X
authors: Zhang
authors: Department of Molecular Genetics and MicrobiologyUniversity of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors: Handong
authors: H
authors: Zheng
authors: Department of Biochemistry and Molecular BiologyUniversity of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors: Xin
authors: X
authors: Yang
authors: Department of Molecular Genetics and MicrobiologyUniversity of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA xyang@salud.unm.edu meilianliu@salud.unm.edu.
authors: Xuexian
authors: X
authors: Yang
authors: Department of Biochemistry and Molecular BiologyUniversity of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA Department of Metabolism and EndocrinologyMetabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China xyang@salud.unm.edu meilianliu@salud.unm.edu.
authors: Meilian
authors: M
authors: Liu
mesh_terms: D002001:Adipose Tissue, Brown / Q000276:immunology*; D052436:Adipose Tissue, White / Q000276:immunology*; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D004804:Eosinophils / Q000502:physiology*; D007113:Immunity, Innate; D000067596:Interleukin-33 / Q000502:physiology*; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D051379:Mice; D009765:Obesity / Q000276:immunology*
chemical_list: D000067596:Interleukin-33
keywords: IL-33; ILC2; eosinophil; obesity; sympathetic tone