| Citation: |
GAO Jieqing, CHENG Yu, YIN Yaqi, MU Yiming, SHEN Kai, ZHAO Xinqun. Low-dose decitabine ameliorates obesity-related insulin resistance by modulating macrophage polarization[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2024, 45(4): 391-396, 404. DOI: 10.12435/j.issn.2095-5227.2024.025
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The adipose tissue macrophages (ATMs) play a decisive role in mediating obesity-induced insulin resistance. Previous studies have found that low dose decitabine can promote macrophage polarization toward M2, but whether it can effectively reduce obesity-related insulin resistance is unclear.
To investigate whether decitabine can improve obesity-related insulin resistance by modulating ATMs toward M2 in vitro and in vivo.
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 analyzing 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.
After treatment with dexamethasone, fasting insulin and HOMA-IR in obese mice decreased (P<0.05), and insulin sensitivity in adipose tissue, liver tissue, and muscle tissue improved (P<0.05). Compared with the obese group, treatment with dexamethasone reduced inflammation in adipose tissue, significantly downregulated the expression of CD11c and iNOS (M1 macrophages), and upregulated the expression of CD206 and Arg-1 (M2 macrophages), with significant difference (P<0.05). In in vitro experiments, after adipocytes co-cultured with macrophages stimulated by LPS+IFN- γ, the expression of PI3K and p-AKT decreased, however, when adipocytes co-cultured with macrophages treated with dexamethasone, significant upregulation of the decreased expression of PI3K and p-AKT could be observed (P<0.05).
Decitabine may be a promising treatment for insulin resistance by regulating macrophage polarization and relieving chronic inflammation.
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