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Mice lacking NKT cells but with a complete complement of CD8+ T-cells are not protected against the metabolic abnormalities of diet-induced obesity.

Mantell BS, Stefanovic-Racic M, Yang X, Dedousis N, Sipula IJ, O'Doherty RM - PLoS ONE (2011)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

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 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.

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Inflammatory marker expression in adipose tissue and liver of wild-type and CD1d  mice.qRT-PCR was used to assess the expression of indicated genes in liver and adipose tissue from high fat fed wild-type (WT) and CD1d  (KO) mice. Results are presented as ΔΔCt (KO/WT) ±SE for a minimum of 5 animals in each group.
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pone-0019831-g006: Inflammatory marker expression in adipose tissue and liver of wild-type and CD1d mice.qRT-PCR was used to assess the expression of indicated genes in liver and adipose tissue from high fat fed wild-type (WT) and CD1d (KO) mice. Results are presented as ΔΔCt (KO/WT) ±SE for a minimum of 5 animals in each group.

Mentions: The inflammatory response in obesity is well described and involves increased expression of TH1 cytokines and macrophage infiltration/activation into adipose tissue and liver[1], [3], [4], [23], [24]. A previous study[13] demonstrated that the combined deletion of CD8+ T-cells and NKT cells reduced adipose tissue inflammation in obesity. However, the effects of NKT deletion alone are unknown. Thus, we next assessed the effects of NKT deletion on the expression of inflammatory markers in WAT and liver of obese CD1d−/− and WT mice. As figure 6 shows, qRT-PCR analysis of TNFα, IL-6, IL-10, IFN-γ, MCP-1 and MIP1α demonstrated that expression of these genes was similar in CD1d−/− and WT animals. These data, taken with the data presented above demonstrate that deletion of NKT cells alone is not sufficient to alter the inflammatory status of obesity.


Mice lacking NKT cells but with a complete complement of CD8+ T-cells are not protected against the metabolic abnormalities of diet-induced obesity.

Mantell BS, Stefanovic-Racic M, Yang X, Dedousis N, Sipula IJ, O'Doherty RM - PLoS ONE (2011)

Inflammatory marker expression in adipose tissue and liver of wild-type and CD1d  mice.qRT-PCR was used to assess the expression of indicated genes in liver and adipose tissue from high fat fed wild-type (WT) and CD1d  (KO) mice. Results are presented as ΔΔCt (KO/WT) ±SE for a minimum of 5 animals in each group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108591&req=5

pone-0019831-g006: Inflammatory marker expression in adipose tissue and liver of wild-type and CD1d mice.qRT-PCR was used to assess the expression of indicated genes in liver and adipose tissue from high fat fed wild-type (WT) and CD1d (KO) mice. Results are presented as ΔΔCt (KO/WT) ±SE for a minimum of 5 animals in each group.
Mentions: The inflammatory response in obesity is well described and involves increased expression of TH1 cytokines and macrophage infiltration/activation into adipose tissue and liver[1], [3], [4], [23], [24]. A previous study[13] demonstrated that the combined deletion of CD8+ T-cells and NKT cells reduced adipose tissue inflammation in obesity. However, the effects of NKT deletion alone are unknown. Thus, we next assessed the effects of NKT deletion on the expression of inflammatory markers in WAT and liver of obese CD1d−/− and WT mice. As figure 6 shows, qRT-PCR analysis of TNFα, IL-6, IL-10, IFN-γ, MCP-1 and MIP1α demonstrated that expression of these genes was similar in CD1d−/− and WT animals. These data, taken with the data presented above demonstrate that deletion of NKT cells alone is not sufficient to alter the inflammatory status of obesity.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

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 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.

Show MeSH
Related in: MedlinePlus