Abstract:
Background The adipose tissue macrophages (ATM) play a decisive role in mediating obesity-induced insulin resistance. Our previous study found that low dose decitabine can promote macrophage polarization toward M2, but whether it can effectively reduce obesity-related insulin resistance is unclear.
Objective To investigate whether decitabine can improve obesity-related insulin resistance by modulating ATMs toward M 2 in vitro and in vivo.
Methods Decitabine was given to mice on high fat diet by intraperitoneally injection once per day for 5 days. Two weeks later, glucose tolerance and insulin resistance were measured. Epididymal fat was extracted for analysing inflammation and infiltrating macrophages in adipose tissue. In vitro, we examined the effects of decitabine-treated macrophages on insulin sensitivity in fully differentiated 3T3-L1 adipocytes.
Results Decitabine significantly promoted insulin sensitivity in obese mice, whereas their body weight was not affected. Decitabine reduced adipocyte size and immune cell infiltration into the adipose tissue and suppressed the expression of pro-inflammatory factors. Moreover, the imbalance in the ratio of M1 to M2 macrophages in the adipose tissue was significantly restored in decitabine-treated mice. In vitro, decitabine-induced M2 macrophages alleviated the insulin resistance caused by classically activated macrophages (M1, pro-inflammatory) in fully differentiated 3T3-L1 adipocytes.
Conclusion Decitabine may be a promising treatment for insulin resistance by regulating macrophage polarization and relieving chronic inflammation.
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