Mantell, BS and Stefanovic-Racic, M and Yang, X and Dedousis, N and Sipula, IJ and O'Doherty, RM
(2011)
mice lacking NKT cells but with a complete complement of CD8<sup>+</sup> T-Cells are not protected against the metabolic abnormalities of diet-induced obesity.
PLoS ONE, 6 (6).
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 O2/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. © 2011 Mantell et al.
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
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Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID |
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Editor | Fadini, Gian Paolo | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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Date: |
10 June 2011 |
Date Type: |
Publication |
Journal or Publication Title: |
PLoS ONE |
Volume: |
6 |
Number: |
6 |
DOI or Unique Handle: |
10.1371/journal.pone.0019831 |
Schools and Programs: |
School of Medicine > Microbiology and Molecular Genetics |
Refereed: |
Yes |
MeSH Headings: |
Adiposity--immunology; Animals; Antigens, CD1d--genetics; Antigens, CD1d--metabolism; Biological Markers--metabolism; Body Weight--immunology; CD8-Positive T-Lymphocytes--immunology; CD8-Positive T-Lymphocytes--metabolism; Diet--adverse effects; Dietary Fats--adverse effects; Eating--immunology; Energy Metabolism--immunology; Gene Expression Regulation--immunology; Glucose Tolerance Test; Inflammation--genetics; Insulin--metabolism; Liver--immunology; Mice; Mice, Inbred BALB C; Natural Killer T-Cells--cytology; Natural Killer T-Cells--immunology; Obesity--etiology; Obesity--immunology; Obesity--metabolism; Obesity--physiopathology |
Other ID: |
NLM PMC3108591 |
PubMed Central ID: |
PMC3108591 |
PubMed ID: |
21674035 |
Date Deposited: |
30 Aug 2012 14:30 |
Last Modified: |
22 Jun 2021 16:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/13864 |
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