title: Role of NKG2D in obesity-induced adipose tissue inflammation and insulin resistance.
abstract: The early events that initiate inflammation in the adipose tissue during obesity are not well defined. It is unclear whether the recruitment of CD8 T cells to the adipose tissue during onset of obesity occurs through antigen-dependent or -independent processes. We have previously shown that interaction between NKG2D (natural-killer group 2, member D) and its ligand Rae-1ε is sufficient to recruit cytotoxic T lymphocytes to the pancreas and induce insulitis. Here, we tested whether NKG2D-NKG2D ligand interaction is also involved in obesity-induced adipose tissue inflammation and insulin resistance. We observed a significant induction of NKG2D ligand expression in the adipose tissue of obese mice, especially during the early stages of obesity. However, mice lacking NKG2D developed similar levels of insulin resistance and adipose tissue inflammation compared to control mice when placed on a high-fat diet. Moreover, overexpression of Rae-1ε in the adipose tissue did not increase immune cell infiltration to the adipose tissue either in the setting of a normal or high-fat diet. These results indicate that, unlike in the pancreas, NKG2D-NKG2D ligand interaction does not play a critical role in obesity-induced inflammation in the adipose tissue.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Jun-Jae
authors.initials: JJ
authors.lastname: Chung
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Markiewicz
authors.affiliation: Department of Histology and Embryology, University of Rijeka School of Medicine, Rijeka, Croatia.
authors.forename: Bojan
authors.initials: B
authors.lastname: Polić
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America; Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Shaw
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics*; D008024:Ligands; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics* / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015434:Panniculitis / Q000209:etiology*; D011485:Protein Binding; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
chemical_list: D007328:Insulin; C527086:Klrk1 protein, mouse; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D034521:Nuclear Matrix-Associated Proteins; D029543:Nucleocytoplasmic Transport Proteins; C490521:Rae1 protein, mouse; D014409:Tumor Necrosis Factor-alpha