Abstract:

Objective: Luteolin is a natural flavonoid abundant in many edible plants. The aim of this study is to explore
the effect of luteolin (LU) on obesity-associated adipose tissue macrophage (ATM) polarization and its underlying
mechanisms. Methods: Five-week-old C57BL/6 mice were fed with low-fat diet (LFD), high-fat diet (HFD), or HFD with
0.0l% luteolin (HFD＋0.0l% LU) for 12 weeks, respectively. Macrophage infiltration and polarization were detected by
immunohistochemical staining or real-time PCR in epididymal adipose tissue. The in vitro effect of luteolin on RAW264.7
macrophage inflammation and polarization in lipopolysaccharide (LPS) and/or PMA-stimulated conditions was also
explored. The expression levels of proinflammatory cytokines and M1/M2 marker genes were detected by real-time PCR.
Results: Dietary luteolin reduced HFD-induced ATM infiltration and mRNA levels of M1 macrophage marker genes. In LPSstimulated
conditions, luteolin inhibited the expression of proinflammatory cytokines and M1 marker genes in RAW264.7
macrophages. In contrast, the expression of M2 marker genes was enhanced by luteolin. However, these effects of luteolin
were aborted by protein kinase C (PKC) activator phorbol myristate acetate (PMA). Conclusion: Luteolin can inhibit obesityassociated
ATM and RAW264.7 macrophage polarization in LPS stimulated-conditions through protein kinase C pathway.

Key words: luteolin, obesity, macrophage, protein kinase C