title: Human primary adipocytes exhibit immune cell function: adipocytes prime inflammation independent of macrophages.
abstract: BACKGROUND
  Obesity promotes inflammation in adipose tissue (AT) and this is implicated in pathophysiological complications such as insulin resistance, type 2 diabetes and cardiovascular disease. Although based on the classical hypothesis, necrotic AT adipocytes (ATA) in obese state activate AT macrophages (ATM) that then lead to a sustained chronic inflammation in AT, the link between human adipocytes and the source of inflammation in AT has not been in-depth and systematically studied. So we decided as a new hypothesis to investigate human primary adipocytes alone to see whether they are able to prime inflammation in AT.
  
  
  RESULTS
  Using mRNA expression, human preadipocytes and adipocytes express the cytokines/chemokines and their receptors, MHC II molecule genes and 14 acute phase reactants including C-reactive protein. Using multiplex ELISA revealed the expression of 50 cytokine/chemokine proteins by human adipocytes. Upon lipopolysaccharide stimulation, most of these adipocyte-associated cytokines/chemokines and immune cell modulating receptors were up-regulated and a few down-regulated such as (ICAM-1, VCAM-1, MCP-1, IP-10, IL-6, IL-8, TNF-α and TNF-β highly up-regulated and IL-2, IL-7, IL-10, IL-13 and VEGF down-regulated. In migration assay, human adipocyte-derived chemokines attracted significantly more CD4+ T cells than controls and the number of migrated CD4+ cells was doubled after treating the adipocytes with LPS. Neutralizing MCP-1 effect produced by adipocytes reduced CD4+ migration by approximately 30%.
  
  
  CONCLUSIONS
  Human adipocytes express many cytokines/chemokines that are biologically functional. They are able to induce inflammation and activate CD4+ cells independent of macrophages. This suggests that the primary event in the sequence leading to chronic inflammation in AT is metabolic dysfunction in adipocytes, followed by production of immunological mediators by these adipocytes, which is then exacerbated by activated ATM, activation and recruitment of immune cells. This study provides novel knowledge about the prime of inflammation in human obese adipose tissue, opening a new avenue of investigations towards obesity-associated type 2 diabetes.
authors: Center for Medical Biomics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Kees
authors: K
authors: Meijer
authors: Marcel
authors: M
authors: de Vries
authors: Saad
authors: S
authors: Al-Lahham
authors: Marcel
authors: M
authors: Bruinenberg
authors: Desirée
authors: D
authors: Weening
authors: Martijn
authors: M
authors: Dijkstra
authors: Niels
authors: N
authors: Kloosterhuis
authors: Roelof Jan
authors: RJ
authors: van der Leij
authors: Han
authors: H
authors: van der Want
authors: Bart-Jan
authors: BJ
authors: Kroesen
authors: Roel
authors: R
authors: Vonk
authors: Farhad
authors: F
authors: Rezaee
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology* / Q000276:immunology* / Q000648:ultrastructure; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D040901:Proteomics; D019707:Receptors, Chemokine / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D018925:Chemokines; D000949:Histocompatibility Antigens Class II; D019707:Receptors, Chemokine