title: Deletion of CD1d in Adipocytes Aggravates Adipose Tissue Inflammation and Insulin Resistance in Obesity.
abstract: Adipose tissue inflammation is an important factor in obesity that promotes insulin resistance. Among various cell types in adipose tissue, immune cells actively regulate inflammatory responses and affect whole-body energy metabolism. In particular, invariant natural killer T (iNKT) cells contribute to mitigating dysregulation of systemic energy homeostasis by counteracting obesity-induced inflammation in adipose tissue. However, the molecular mechanisms by which adipose iNKT cells become activated and mediate anti-inflammatory roles in obese adipose tissue have not been thoroughly understood yet. In the current study, we demonstrate that adipocyte CD1d plays a key role in the stimulation of adipose iNKT cells, leading to anti-inflammatory responses in high-fat diet (HFD)-fed mice. Accordingly, adipocyte-specific CD1d-knockout (CD1dADKO) mice showed reduced numbers of iNKT cells in adipose tissues and decreased responses to α-galactosylceramide-induced iNKT cell activation. Additionally, HFD-fed CD1dADKOmice revealed reduced interleukin-4 expression in adipose iNKT cells and aggravated adipose tissue inflammation and insulin resistance. Collectively, these data suggest that adipocytes could selectively stimulate adipose iNKT cells to mediate anti-inflammatory responses and attenuate excess proinflammatory responses in obese adipose tissue.
authors.affiliation: School of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Huh
authors.affiliation: School of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea.
authors.forename: Jeu
authors.initials: J
authors.lastname: Park
authors.affiliation: School of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea.
authors.forename: Jong In
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Department of Biophysics and Chemical Biology, Seoul National University, Seoul, Korea.
authors.forename: Yoon Jeong
authors.initials: YJ
authors.lastname: Park
authors.affiliation: School of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea.
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Lee
authors.affiliation: School of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea jaebkim@snu.ac.kr.
authors.forename: Jae Bum
authors.initials: JB
authors.lastname: Kim
mesh_terms: D017667:Adipocytes / Q000276:immunology*; D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology*; D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation; D059305:Diet, High-Fat; D004734:Energy Metabolism; D005434:Flow Cytometry; D007249:Inflammation; D007333:Insulin Resistance / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D009765:Obesity / Q000235:genetics / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D055610:Antigens, CD1d; C584692:CD1d antigen, mouse; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; C577686:interleukin-6, mouse; D015847:Interleukin-4