title: Activation of natural killer T cells promotes M2 Macrophage polarization in adipose tissue and improves systemic glucose tolerance via interleukin-4 (IL-4)/STAT6 protein signaling axis in obesity.
abstract: Natural killer T (NKT) cells are important therapeutic targets in various disease models and are under clinical trials for cancer patients. However, their function in obesity and type 2 diabetes remains unclear. Our data show that adipose tissues of both mice and humans contain a population of type 1 NKT cells, whose abundance decreases with increased adiposity and insulin resistance. Although loss-of-function of NKT cells had no effect on glucose tolerance in animals with prolonged high fat diet feeding, activation of NKT cells by lipid agonist α-galactosylceramide enhances alternative macrophage polarization in adipose tissue and improves glucose homeostasis in animals at different stages of obesity. Furthermore, the effect of NKT cells is largely mediated by the IL-4/STAT6 signaling axis in obese adipose tissue. Thus, our data identify a novel therapeutic target for the treatment of obesity-associated inflammation and type 2 diabetes.
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Yewei
authors.initials: Y
authors.lastname: Ji
authors.forename: Shengyi
authors.initials: S
authors.lastname: Sun
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.forename: Prerna
authors.initials: P
authors.lastname: Bhargava
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.forename: Karen S L
authors.initials: KS
authors.lastname: Lam
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Lee
authors.forename: Sander
authors.initials: S
authors.lastname: Kersten
authors.forename: Ling
authors.initials: L
authors.lastname: Qi
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000328:Adult; D000818:Animals; D015992:Body Mass Index; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006017:Glycolipids / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism
chemical_list: D006017:Glycolipids; D005947:Glucose