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

Recruitment of immune cells to adipose tissue is altered dramatically in obesity, which results in chronic inflammation ofthe adipose tissue that leads to metabolic disorders, such as insulin resistance and type 2 diabetes mellitus. The regulationof immune cell infiltration into adipose tissue has prophylactic and therapeutic implications for obesity-related diseases. Wepreviously showed that naringenin, a citrus flavonoid, suppressed macrophage infiltration into adipose tissue by inhibitingmonocyte 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 neutrophilsalso infiltrate into adipose tissue in the progression phase to obesity. Naringenin suppressed neutrophil infiltration into adiposetissue induced by the short-term (2 weeks) feeding of a HFD to mice. Naringenin tended to inhibit the HFD-inducedexpression of several chemokines, including MCP-1 and MCP-3, in adipose tissue. Naringenin also inhibited MCP-3 expressionin 3T3-L1 adipocytes and a co-culture of 3T3-L1 adipocytes and RAW264 macrophages. However, naringenin did notaffect the expression of macrophage inflammatory protein-2 (MIP-2), an important chemokine for neutrophil migration andactivation, in macrophages or in a co-culture of adipocytes and macrophages. Our results suggest that naringenin suppressesneutrophil infiltration into adipose tissue via the regulation of MCP-3 expression and macrophage infiltration.九州保健福祉大学201