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Functional role of natural killer T cells in non-obese pre-diabetes model mice.

ABSTRACT: Pre-diabetic patients have a high risk of developing diabetes as well as other associated diseases. From the viewpoint of risk assessment and to assist the development of protective therapies, we focused on the functional role of natural killer T (NKT) cells in pre-diabetes. We found that the expression of an NKT cell marker gene, Va14-Ja18, was significantly lower in specific tissues/organs such as adipose tissue and pancreas in non-obese pre-diabetes model mice than in their normal littermates. Subsequently, in the pre-diabetes model mice, Va14-Ja18 was activated with ?-galactosylceramide (?-GalCer) and its effect on glucose tolerance was estimated. The simultaneous injection of ?-GalCer and lymphocytes improved glucose tolerance with its maximum effect on the 3rd day. An analysis of circulating cytokine levels revealed that interferon-?, which is a pro-inflammatory cytokine, was secreted only on the 1st day after treatment with ?-GalCer and that interleukin (IL)-4, which is an anti-inflammatory cytokine, was secreted from the 1st to the 4th day. The prolonged secretion of IL-4 was thought to substantially contribute to the improvement of glucose tolerance. Based on these results, the functional role of NKT cells in pre-diabetes is to improve metabolic dysfunctions.

SUBMITTER: Saito M

PROVIDER: S-EPMC5809671 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Functional role of natural killer T cells in non-obese pre-diabetes model mice.

Saito Mikako M Kaburagi Misako M Otokuni Keiko K Takahashi Genu G

Cytotechnology 20171102 1

Pre-diabetic patients have a high risk of developing diabetes as well as other associated diseases. From the viewpoint of risk assessment and to assist the development of protective therapies, we focused on the functional role of natural killer T (NKT) cells in pre-diabetes. We found that the expression of an NKT cell marker gene, Va14-Ja18, was significantly lower in specific tissues/organs such as adipose tissue and pancreas in non-obese pre-diabetes model mice than in their normal littermates ...[more]

PMID: 29098499

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Project description:Background: The association of obesity and an increased risk for severe infections and various cancer types is well-described. Natural killer (NK) cells are circulating lymphoid cells and promoters of the immune response toward viruses and malignant cells. As demonstrated in previous studies the phenotype and functionality of NK cells is impaired in obesity. So far, the majority of animal studies were exclusively performed using ad libitum feeding regimes and it remained unclear whether NK cell alterations are mediated by obesity-associated immunological changes or by direct effects of the dietary composition. Therefore, the aim of the present study was to characterize NK cells in the peripheral blood of obese-resistant BALB/c mice supplied a normal-fat diet (NFD) or high-fat diet (HFD), ad libitum or in a restrictive manner. Methods: Twenty-eight BALB/c-mice were fed a NFD or HFD either ad libitum or in a restrictive feeding regime with 90% of the mean daily diet supply of the corresponding ad libitum group (each group n = 7). Blood and visceral adipose tissue were collected for flow cytometric analysis, analysis of plasma cytokine concentrations by multiplex immunoassay and real-time RT-PCR analyses. For statistical analyses two-way ANOVA with the factors "feeding regime" and "diet" was performed followed by a post-hoc Tukey's multiple comparison test and to compare means of the four mouse groups. Results: Ad libitum-feeding of a HFD in BALB/c mice has no influence on body weight gain, visceral fat mass, plasma cytokine concentrations, immune cell populations as well as the number, frequency and phenotype of NK cells. In contrast, restrictive feeding of a HFD compared to NFD led to significantly higher body weights, visceral fat mass and plasma interferon-γ concentrations which was associated with changes in the frequencies of granulocytes and NK cell subsets as well as in the surface expression of NK cell maturation markers. Conclusion: Results demonstrate for the first time that HFD-induced alterations in NK cells are consequences of the obese associated immunological profile rather than a direct effect of the dietary composition. These data can help to clarify the increased risk for cancer and severe infections in obesity.

Dataset Information

Functional role of natural killer T cells in non-obese pre-diabetes model mice.

Publications

Functional role of natural killer T cells in non-obese pre-diabetes model mice.

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