title: Large adipocytes function as antigen-presenting cells to activate CD4(+) T cells via upregulating MHCII in obesity.
abstract: OBJECTIVE
  Although obesity is associated with low-grade inflammation and metabolic disorders, clinical studies suggested some obese people were metabolically healthy with smaller adipocyte size compared with metabolically abnormal obese (MAO). This indicated adipocyte size may be an important predictor underlay the distinction between MAO and metabolically healthy obese. As recent study has shown that adipocytes expressed class II major histocompatibility complex (MHCII), which functioned as APCs during obesity. However, the relationship between adipocyte hypertrophy and MHCII expression was not involved. Here we hypothesize that hypertrophic adipocytes could be associated with upregulating MHCII to influence adipose tissue metabolism.
  
  
  METHODS
  Adipocytes were sorted by fluorescence-activated cell sorting (FACS) according to the cell size from MAO mice. The activation of MHCII, T cells and related signaling molecules were examined by FACS, ELISA and western blotting. 3T3-L1 cell line and primary adipocytes were used to examine the effect of free fatty acids (FFA) on adipocytes enlargement and MHCII expression.
  
  
  RESULTS
  MAO mice had a significant increase in adipocytes size and FFA concentration. The large adipocytes from both obese and non-obese mice expressed higher levels of MHCII than small adipocytes. Importantly, large adipocytes from obese mice stimulated CD4(+) T cells to secrete more interferon (IFN)-γ. Furthermore, the activation of the JNK-STAT1 pathway was involved in upregulation of MHCII in large adipocytes. In vitro FFA treatment promoted adipocyte hypertrophy and expression of MHCII-associated genes.
  
  
  CONCLUSIONS
  This study demonstrates that large adipocytes highly express MHCII and function as APC to stimulate IFN-γ-expressing CD4(+) T cells, in which FFA may have important roles before IFN-γ elevated. These findings suggest that adipocyte hypertrophy, rather than overall obesity, is the major contributor to adipose tissue inflammation and insulin resistance.
authors.affiliation: Key Laboratory of Metabolic Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Basic Medical School, Shanghai, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Department of Immunology, Fudan University Basic Medical School, Shanghai, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Department of Immunology, Fudan University Basic Medical School, Shanghai, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Key Laboratory of Metabolic Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Basic Medical School, Shanghai, PR China.
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.affiliation: Key Laboratory of Metabolic Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Basic Medical School, Shanghai, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Metabolic Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Basic Medical School, Shanghai, PR China.
authors.forename: S
authors.initials: S
authors.lastname: Qian
authors.affiliation: Key Laboratory of Metabolic Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Basic Medical School, Shanghai, PR China.
authors.forename: Q
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Department of Immunology, Fudan University Basic Medical School, Shanghai, PR China.
authors.forename: R
authors.initials: R
authors.lastname: He
authors.affiliation: Key Laboratory of Metabolic Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Basic Medical School, Shanghai, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Li
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D004195:Disease Models, Animal; D005802:Genes, MHC Class II / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D007333:Insulin Resistance; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000276:immunology* / Q000473:pathology*; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D007371:Interferon-gamma