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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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CLAMS analysis.High fat fed wild-type (WT) and CD1d  (KO) mice underwent CLAMS analysis as described in Methods. Data for VO2 (Panels A and B), and ambulatory activity (Panel C) are presented. Results are presented as the means±SE for 4 animals in each group.
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pone-0019831-g003: CLAMS analysis.High fat fed wild-type (WT) and CD1d (KO) mice underwent CLAMS analysis as described in Methods. Data for VO2 (Panels A and B), and ambulatory activity (Panel C) are presented. Results are presented as the means±SE for 4 animals in each group.

Mentions: The CD1d−/− mouse lacks NKT cells but has a normal complement of CD8+ T-cells ([18], [19] and Figure 2E). CD1d−/− mice and littermate wild-type controls (WT), on a pure C57BL/6J background, were exposed to a high fat diet, and a number of metabolic variables were assessed. Weight gain, caloric intake, and body composition were unaffected by NKT cell deletion (Figure 2A–D). Furthermore, indirect calorimetry demonstrated that metabolic rate and activity were similar in CD1d−/− and WT mice (Figure 3A–C), as would be expected given the lack of an effect on NKT depletion on body composition and caloric intake.


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)

CLAMS analysis.High fat fed wild-type (WT) and CD1d  (KO) mice underwent CLAMS analysis as described in Methods. Data for VO2 (Panels A and B), and ambulatory activity (Panel C) are presented. Results are presented as the means±SE for 4 animals in each group.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0019831-g003: CLAMS analysis.High fat fed wild-type (WT) and CD1d (KO) mice underwent CLAMS analysis as described in Methods. Data for VO2 (Panels A and B), and ambulatory activity (Panel C) are presented. Results are presented as the means±SE for 4 animals in each group.
Mentions: The CD1d−/− mouse lacks NKT cells but has a normal complement of CD8+ T-cells ([18], [19] and Figure 2E). CD1d−/− mice and littermate wild-type controls (WT), on a pure C57BL/6J background, were exposed to a high fat diet, and a number of metabolic variables were assessed. Weight gain, caloric intake, and body composition were unaffected by NKT cell deletion (Figure 2A–D). Furthermore, indirect calorimetry demonstrated that metabolic rate and activity were similar in CD1d−/− and WT mice (Figure 3A–C), as would be expected given the lack of an effect on NKT depletion on body composition and caloric intake.

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