title: Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice.
abstract: It has been shown that CD1d expression and glycolipid-reactive, CD1d-restricted NKT cells exacerbate the development of obesity and insulin resistance in mice. However, the relevant CD1d-expressing cells that influence the effects of NKT cells on the progression of obesity remain incompletely defined. In this study, we have demonstrated that 3T3-L1 adipocytes can present endogenous ligands to NKT cells, leading to IFN-γ production, which in turn, stimulated 3T3-L1 adipocytes to enhance expression of CD1d and CCL2, and decrease expression of adiponectin. Furthermore, adipocyte-specific CD1d deletion decreased the size of the visceral adipose tissue mass and enhanced insulin sensitivity in mice fed a high-fat diet (HFD). Accordingly, NKT cells were less activated, IFN-γ production was significantly reduced, and levels of adiponectin were increased in these animals as compared with control mice on HFD. Importantly, macrophage recruitment into the adipose tissue of adipocyte-specific CD1d-deficient mice was significantly blunted. These findings indicate that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity.
authors.affiliation: Department of Immunology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Satoh
authors.affiliation: Department of Immunology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Hoshino
authors.affiliation: Department of Immunology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Fujita
authors.affiliation: Department of Immunology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Misao
authors.initials: M
authors.lastname: Iizuka
authors.affiliation: Department of Laboratory Medicine, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Department of Emergency Medicine, Tufts Medical Center, Lowell General Hospital, Boston, MA 02111, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Clingan
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.affiliation: Department of Immunology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwabuchi
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000276:immunology*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation; D055610:Antigens, CD1d / Q000235:genetics / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D018450:Disease Progression; D005699:Galactosylceramides / Q000276:immunology; D007333:Insulin Resistance / Q000276:immunology / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000276:immunology; D009765:Obesity / Q000209:etiology* / Q000276:immunology* / Q000517:prevention & control
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D055610:Antigens, CD1d; D018122:B7-1 Antigen; C584692:CD1d antigen, mouse; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D007371:Interferon-gamma