Carbon monoxide reverses adipose tissue inflammation and insulin resistance upon loss of ovarian function
Carbon monoxide reverses adipose tissue inflammation and insulin resistance upon loss of ovarian function
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DOI：
10.1152/ajpendo.00458.2014
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发表时间：
2015-04-15
影响因子：
5.1
通讯作者：
Choi, Hye-Seon
中科院分区：
文献类型：
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作者：
Choi, Eun-Kyung;Park, Hyun-Jung;Choi, Hye-Seon
我们假设一氧化碳（CO）可能抑制慢性炎症，导致代谢紊乱。在小鼠中进行卵巢切除术（OVX）以模拟继发于卵巢功能丧失的慢性炎症。OVX增加了脂肪量和高度炎症性CD 11 c细胞浸润到脂肪组织（AT）中，导致葡萄糖代谢紊乱。CO的治疗减弱了这些; CO减少了AT中表达CD 11 c的细胞的募集，并减少了骨髓源性巨噬细胞中CD 11 c的表达，保护它们免受M1极化。上调cGMP和减少活性氧负责CO对CD 11 c表达的抑制活性;使用小干扰RNA敲低可溶性鸟苷酸环化酶或血红素加氧酶-1大幅降低了这种抑制。CO改善OVX诱导的胰岛素抵抗（IR）与其减轻AT炎症的活性高度相关。我们的研究结果表明，CO通过减少AT炎症来治疗绝经后IR。
We hypothesized that carbon monoxide (CO) might suppress chronic inflammation, which led to metabolic disturbances. Ovariectomy (OVX) was performed in mice to mimic chronic inflammation secondary to loss of ovarian function. OVX increased fat mass and the infiltration of highly inflammatory CD11c cells into adipose tissue (AT), resulting in a disturbance of glucose metabolism. Treatment of CO attenuated these; CO decreased recruitment of CD11c-expressing cells in AT and reduced expression of CD11c in bone marrow-derived macrophages, protecting them from M1 polarization. Upregulated cGMP and decreased reactive oxygen species were responsible for the inhibitory activity of CO on CD11c expression; knockdown of soluble guanylate cyclase or heme oxygenase-1 using small interfering RNAs reduced this inhibition substantially. Improved OVX-induced insulin resistance (IR) by CO was highly associated with its activity to attenuate AT inflammation. Our results suggest a therapeutic value of CO to treat postmenopausal IR by reducing AT inflammation.