Naringenin suppresses neutrophil infiltration into adipose tissue in high-fat diet-induced obese mice
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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.
KeywordsNaringenin Obesity Neutrophil Macrophage MCP-3 MIP-2
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.
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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Conflict of interest
The authors declare that they have no conflict of interest.
- 9.Kintscher U, Hartge M, Hess K, Foryst-Ludwig A, Clemenz M, Wabitsch M, Fischer-Posovszky P, Barth TF, Dragun D, Skurk T, Hauner H, Bluher M, Unger T, Wolf AM, Knippschild U, Hombach V, Marx N (2008) T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol 28:1304–1310CrossRefGoogle Scholar
- 14.Pinho-Ribeiro FA, Zarpelon AC, Mizokami SS, Borghi SM, Bordignon J, Silva RL, Cunha TM, Alves-Filho JC, Cunha FQ, Casagrande R, Verri WA Jr (2016) The citrus flavonone naringenin reduces lipopolysaccharide-induced inflammatory pain and leukocyte recruitment by inhibiting NF-kappaB activation. J Nutr Biochem 33:8–14CrossRefGoogle Scholar
- 19.Bertola A, Ciucci T, Rousseau D, Bourlier V, Duffaut C, Bonnafous S, Blin-Wakkach C, Anty R, Iannelli A, Gugenheim J, Tran A, Bouloumie A, Gual P, Wakkach A (2012) Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients. Diabetes 61:2238–2247CrossRefGoogle Scholar
- 21.Xu LL, McVicar DW, Ben-Baruch A, Kuhns DB, Johnston J, Oppenheim JJ, Wang JM (1995) Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors: binding and signaling of MCP3 through shared as well as unique receptors on monocytes and neutrophils. Eur J Immunol 25:2612–2617CrossRefGoogle Scholar
- 24.Schiwon M, Weisheit C, Franken L, Gutweiler S, Dixit A, Meyer-Schwesinger C, Pohl JM, Maurice NJ, Thiebes S, Lorenz K, Quast T, Fuhrmann M, Baumgarten G, Lohse MJ, Opdenakker G, Bernhagen J, Bucala R, Panzer U, Kolanus W, Grone HJ, Garbi N, Kastenmuller W, Knolle PA, Kurts C, Engel DR (2014) Crosstalk between sentinel and helper macrophages permits neutrophil migration into infected uroepithelium. Cell 156:456–468CrossRefGoogle Scholar
- 27.Hamalainen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E (2007) Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediat Inflamm 2007:45673CrossRefGoogle Scholar
- 32.Melzig MF, Loser B, Ciesielski S (2001) Inhibition of neutrophil elastase activity by phenolic compounds from plants. Pharmazie 56:967–970Google Scholar