title: Mice lacking NKT cells but with a complete complement of CD8+ T-cells are not protected against the metabolic abnormalities of diet-induced obesity.
abstract: The contribution of natural killer T (NKT) cells to the pathogenesis of metabolic abnormalities of obesity is controversial. While the combined genetic deletion of NKT and CD8(+) T-cells improves glucose tolerance and reduces inflammation, interpretation of these data have been complicated by the recent observation that the deletion of CD8(+) T-cells alone reduces obesity-induced inflammation and metabolic dysregulation, leaving the issue of the metabolic effects of NKT cell depletion unresolved. To address this question, CD1d null mice (CD1d(-/-)), which lack NKT cells but have a full complement of CD8(+) T-cells, and littermate wild type controls (WT) on a pure C57BL/6J background were exposed to a high fat diet, and glucose intolerance, insulin resistance, dyslipidemia, inflammation, and obesity were assessed. Food intake (15.5±4.3 vs 15.3±1.8 kcal/mouse/day), weight gain (21.8±1.8 vs 22.8±1.4 g) and fat mass (18.6±1.9 vs 19.5±2.1 g) were similar in CD1d(-/-) and WT, respectively. As would be expected from these data, metabolic rate (3.0±0.1 vs 2.9±0.2 ml O(2)/g/h) and activity (21.6±4.3 vs 18.5±2.6 beam breaks/min) were unchanged by NKT cell depletion. Furthermore, the degree of insulin resistance, glucose intolerance, liver steatosis, and adipose and liver inflammatory marker expression (TNFα, IL-6, IL-10, IFN-γ, MCP-1, MIP1α) induced by high fat feeding in CD1d(-/-) were not different from WT. We conclude that deletion of NKT cells, in the absence of alterations in the CD8(+) T-cell population, is insufficient to protect against the development of the metabolic abnormalities of diet-induced obesity.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Mantell
authors.forename: Maja
authors.initials: M
authors.lastname: Stefanovic-Racic
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Nikolas
authors.initials: N
authors.lastname: Dedousis
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Sipula
authors.forename: Robert M
authors.initials: RM
authors.lastname: O'Doherty
mesh_terms: D050154:Adiposity / Q000276:immunology; D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D004032:Diet / Q000009:adverse effects*; D004041:Dietary Fats / Q000009:adverse effects; D004435:Eating / Q000276:immunology; D004734:Energy Metabolism / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000235:genetics; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000276:immunology; D009765:Obesity / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D055610:Antigens, CD1d; D015415:Biomarkers; D004041:Dietary Fats; D007328:Insulin