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Adipocyte and Cell Biology

Intracellular ATP in balance of pro- and anti-inflammatory cytokines in adipose tissue with and without tissue expansion

Abstract

Objectives:

To understand the mechanism of white fat expansion in the presence of inflammation, we examined the balance of pro- and anti-inflammatory cytokines in epididymal fat during weight gain in diet-induced obese mice.

Methods:

The pro- and anti-inflammatory cytokines were examined in white fat of diet-induced obese mice and lean mice. The mechanism of gene expression was investigated with a focus on intracellular ATP (iATP). ATP activity was tested in cellular and non-cellular systems in activation of serine kinases (IKKβ, JNK and ERK).

Results:

The pro- (tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), IL-6, monocyte chemoattractant protein 1, interferon gamma and osteopontin) and the anti-inflammatory cytokines (IL-10, IL-1Ra, IL-13, soluble TNF receptor 2, pigment epithelium-derived factor and adiponectin) were increased at the same time during the weight gain. The balance was observed even in the absence of tissue expansion upon feeding in lean and obese mice. The iATP levels were positively associated with the cytokine elevation in the adipose tissue. In macrophages, induction of iATP with lauric acid stimulated the expression. Inhibition of iATP with β-oxidation inhibitor (Etomoxir) or mitochondrial uncoupler (2,4-dinitrophenol, DNP) suppressed the expression. ATP exhibited an activity in the activation of inflammatory kinases (IKKβ, JNK and ERK) in the living cells and cell lysate. The kinase activation was blocked in the cells by ATP inhibition.

Conclusions:

The data suggest that the pro- and anti-inflammatory cytokines are dynamically balanced in the white adipose tissue by iATP.

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Acknowledgements

This work was supported by National Institutes of Health grant R56 DK068036-11 (JY), the National Natural Science Foundation of China (grant number 81370915), Program for Innovative Research Team (in Science and Technology) in University of Henan Province (grant number 15IRTSTHN025) and CNRU (NIH 1P30-DK072476) center grant to the genomic core. The qRT-PCR assay was performed in core facility supported by NIH grant (2P30DK072476). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author contributions

JHL, YZ, ZZ, XZ and XY, conducted the experiments. HW and JY designed the study and prepared the manuscript. All authors read and approved the final manuscript.

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Correspondence to J Ye.

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The authors declare no conflict of interest.

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Supplementary Information accompanies this paper on International Journal of Obesity website

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Lee, J., Zhang, Y., Zhao, Z. et al. Intracellular ATP in balance of pro- and anti-inflammatory cytokines in adipose tissue with and without tissue expansion. Int J Obes 41, 645–651 (2017). https://doi.org/10.1038/ijo.2017.3

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  • DOI: https://doi.org/10.1038/ijo.2017.3

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