Overexpression of cyclooxygenase-2 in adipocytes reduces fat accumulation in inguinal white adipose tissue and hepatic steatosis in high-fat fed mice
Overexpression of cyclooxygenase-2 in adipocytes reduces fat accumulation in inguinal white adipose tissue and hepatic steatosis in high-fat fed mice
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DOI：
10.1038/s41598-019-45062-w
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发表时间：
2019-06-20
影响因子：
4.6
通讯作者：
Kristiansen, Karsten
中科院分区：
文献类型：
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作者：
Danneskiold-Samsoe, Niels Banhos;Sonne, Si Brask;Kristiansen, Karsten
环氧合酶是代谢和免疫过程的重要调节剂，通过将C20脂肪酸转化为各种调节性脂质介质，环氧合酶活性与白色脂肪组织的布朗宁有关。我们产生了在成熟脂肪细胞中表达编码环氧合酶-2（考克斯-2）的Ptgs 2基因的转基因（TG）C57 BL/6小鼠。高脂饮食喂养的TG小鼠体重增加略低，肝脏脂肪变性较少，胰岛素敏感性略有改善，但葡萄糖耐量无差异。与同窝野生型小鼠相比，TG小鼠选择性减少腹股沟白色脂肪组织（iWAT）质量和脂肪细胞大小，而附睾（eWAT）脂肪库保持不变。iWAT的变化伴随着特异性COX衍生脂质介质水平的增加以及白细胞介素-33、白细胞介素-4和精氨酸酶-1 mRNA水平的增加，但解偶联蛋白1的表达并未增加或能量消耗增加。TG小鼠的附睾WAT（eWAT）除了嗜酸性粒细胞浸润增加外，几乎没有变化。我们的研究结果表明，脂肪细胞的考克斯-2衍生的脂质介质在介导与减少肝脂肪变性相关的皮下WAT中的2型免疫信号中发挥作用，但没有伴随诱导布朗宁和增加能量消耗。
Cyclooxygenases are known as important regulators of metabolism and immune processes via conversion of C20 fatty acids into various regulatory lipid mediators, and cyclooxygenase activity has been implicated in browning of white adipose tissues. We generated transgenic (TG) C57BL/6 mice expressing the Ptgs2 gene encoding cyclooxygenase-2 (COX-2) in mature adipocytes. TG mice fed a high-fat diet displayed marginally lower weight gain with less hepatic steatosis and a slight improvement in insulin sensitivity, but no difference in glucose tolerance. Compared to littermate wildtype mice, TG mice selectively reduced inguinal white adipose tissue (iWAT) mass and fat cell size, whereas the epididymal (eWAT) fat depot remained unchanged. The changes in iWAT were accompanied by increased levels of specific COX-derived lipid mediators and increased mRNA levels of interleukin-33, interleukin-4 and arginase-1, but not increased expression of uncoupling protein 1 or increased energy expenditure. Epididymal WAT (eWAT) in TG mice exhibited few changes except from increased infiltration with eosinophils. Our findings suggest a role for COX-2-derived lipid mediators from adipocytes in mediating type 2 immunity cues in subcutaneous WAT associated with decreased hepatic steatosis, but with no accompanying induction of browning and increased energy expenditure.