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IL-25 directly modulates adipocyte function and inflammation through the regulation of adiponectin

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Abstract

Objective

This study aimed to investigate the direct role of IL-25 in modulating adipocyte function during homeostasis and low-grade inflammation induced by lipopolysaccharide (LPS).

Methods

The 3T3-L1 preadipocyte cell lines and primary cultures of adipose-derived stromal vascular precursor cells of wild-type and IL-17RB-deficient mice were used to determine the direct function of IL-25. The expression of IL-17RB in differentiating adipocyte was determined using real-time PCR and flow cytometry analysis. The effect of IL-25 on lipid accumulation, triglyceride content, lipolysis, glucose uptake, and adipokine expression in the mature adipocytes was evaluated. IL-25 modulating the expression of inflammatory cytokines in adipocytes induced by low dose LPS was determined using real-time PCR and ELISA.

Results

The receptor for IL-25 was up-regulated during adipocyte differentiation and IL-25 directly modulated adipocyte function by reducing lipid accumulation and triglyceride concentration and enhancing lipolysis without affecting an insulin-stimulated glucose uptake. Interestingly, IL-25 induced adiponectin secretion through the PI3K/AKT signaling pathway. In 3T3-L1 adipocytes under low-grade inflammation, IL-25 attenuated the expression of IL-6 and CCL5 through the induction of adiponectin.

Conclusion

Our studies suggest that IL-25 directly regulates adipocyte function by maintaining the adiponectin level during homeostasis and by alleviating inflammatory response through the regulation of adiponectin during low-grade inflammation in adipocytes.

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Acknowledgements

This study was supported by Thammasat University Research Fund, Contract No. TUFT 036/2563 and the Thammasat University Research Unit in Molecular Pathogenesis and Immunology of Infectious Diseases; S.J. was supported by the Office of Research Administration, Ph.D. scholarship from Thammasat University. The authors thank the Faculty of Allied Health Sciences and the Center of Scientific Equipment for Advanced Research, Thammasat University for their support.

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Authors and Affiliations

  1. Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, 12120, Thailand

    Siranart Jeerawattanawart, Pilaiwan Siripurkpong & Pornpimon Angkasekwinai

  2. Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, 12120, Thailand

    Siranart Jeerawattanawart

  3. Functional Proteomics Technology Laboratory, Functional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, 12120, Thailand

    Sittiruk Roytrakul

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  1. Siranart Jeerawattanawart
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  4. Pornpimon Angkasekwinai
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Contributions

SJ contributed to experimental design, experimental work, data analysis, and manuscript preparation. SR contributed to conceptualization and experimental design. PS contributed to conceptualization, experimental design, and providing the mouse embryonic fibroblast cell lines 3T3-L1 (3T3-L1 cell, ATCC CL-173). PA contributed to funding acquisition, project supervision, experiment design, experimental work, data analysis, and manuscript preparation.

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Correspondence to Pornpimon Angkasekwinai.

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The authors declared no conflicting financial interests.

Ethical approval

All animal experiments were approved by the Thammasat University Animal Care and Use Committee (008/2562) and performed in accordance with the relevant guidelines and regulations and carried out in compliance with the ARRIVE guidelines (https://arriveguidelines.org).

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Jeerawattanawart, S., Siripurkpong, P., Roytrakul, S. et al. IL-25 directly modulates adipocyte function and inflammation through the regulation of adiponectin. Inflamm. Res. 71, 1229–1244 (2022). https://doi.org/10.1007/s00011-022-01606-x

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