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Naringenin suppresses neutrophil infiltration into adipose tissue in high-fat diet-induced obese mice

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Abstract

Recruitment of immune cells to adipose tissue is altered dramatically in obesity, which results in chronic inflammation of the adipose tissue that leads to metabolic disorders, such as insulin resistance and type 2 diabetes mellitus. The regulation of immune cell infiltration into adipose tissue has prophylactic and therapeutic implications for obesity-related diseases. We previously showed that naringenin, a citrus flavonoid, suppressed macrophage infiltration into adipose tissue by inhibiting monocyte chemoattractant protein-1 (MCP-1) expression in the progression phase to high-fat diet (HFD)-induced obesity. In the current study, we evaluated the effects of naringenin on neutrophil infiltration into adipose tissue, because neutrophils also infiltrate into adipose tissue in the progression phase to obesity. Naringenin suppressed neutrophil infiltration into adipose tissue induced by the short-term (2 weeks) feeding of a HFD to mice. Naringenin tended to inhibit the HFD-induced expression of several chemokines, including MCP-1 and MCP-3, in adipose tissue. Naringenin also inhibited MCP-3 expression in 3T3-L1 adipocytes and a co-culture of 3T3-L1 adipocytes and RAW264 macrophages. However, naringenin did not affect the expression of macrophage inflammatory protein-2 (MIP-2), an important chemokine for neutrophil migration and activation, in macrophages or in a co-culture of adipocytes and macrophages. Our results suggest that naringenin suppresses neutrophil infiltration into adipose tissue via the regulation of MCP-3 expression and macrophage infiltration.

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Acknowledgements

We are grateful to Ms. Yukiko Shimoda and the members of our laboratory (Department of Biochemistry, Kyushu University of Health and Welfare) for their kind support and helpful suggestions. We thank Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

Funding

This work was supported in part by a Grant-in-Aid for Scientific Research (Grant No. JP15K18949 to H. Yoshida) from the Japan Society for the Promotion of Science, by a Nagai Memorial Research Scholarship (Grant No. N-177401 to R. Tsuhako) from the Pharmaceutical Society of Japan, and by a Research Grant (Grant No. H30-06 to H. Yoshida) from Kyushu University of Health and Welfare.

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Authors and Affiliations

  1. Department of Biochemistry, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare, 1714-1 Yoshino, Nobeoka, Miyazaki, 882-8508, Japan

    Rika Tsuhako, Hiroki Yoshida, Chihiro Sugita & Masahiko Kurokawa

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  1. Rika Tsuhako
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  2. Hiroki Yoshida
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Correspondence to Hiroki Yoshida.

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Tsuhako, R., Yoshida, H., Sugita, C. et al. Naringenin suppresses neutrophil infiltration into adipose tissue in high-fat diet-induced obese mice. J Nat Med 74, 229–237 (2020). https://doi.org/10.1007/s11418-019-01332-5

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