COX-2 Deficiency Promotes White Adipogenesis via PGE2-Mediated Paracrine Mechanism and Exacerbates Diet-Induced Obesity.
COX-2 Deficiency Promotes White Adipogenesis via PGE2-Mediated Paracrine Mechanism and Exacerbates Diet-Induced Obesity.
复制标题
作者：
环氧合酶-2（考克斯-2）通过产生前列腺素（PGs）和其他脂质介质，在调节天然免疫和代谢中起重要作用。然而，脂肪考克斯-2在肥胖中的意义仍然很大程度上未知。使用脂肪细胞特异性考克斯-2敲除（KO）小鼠，我们发现，消耗脂肪细胞中的考克斯-2促进了白色脂肪组织的发育，伴随着脂肪细胞的大小和数量的增加，易患饮食诱导的肥胖症、肥胖症和胰岛素抵抗。在脂肪细胞分化过程中，前列腺素E2（PGE 2）可逆转考克斯-2 KO引起的脂肪细胞大小和数量的增加，而PGI 2和PGD 2则不能逆转。在脂肪形成的早期阶段，PGE 2通过PKA途径抑制PPARγ表达，并且PGE 2或PKA激活剂异丙肾上腺素处理减少了考克斯-2 KO原代脂肪细胞中增加的脂滴大小和数量。给予PGE 2可减弱考克斯-2缺陷小鼠脂肪量和脂肪百分比的增加。综上所述，我们的研究证实了脂肪细胞考克斯-2对脂肪生成的抑制作用，并揭示了考克斯-2通过PGE 2介导的旁分泌机制抑制脂肪组织扩张，并防止肥胖和相关代谢紊乱的发展。
Cyclooxygenase-2 (COX-2) plays a critical role in regulating innate immunity and metabolism by producing prostaglandins (PGs) and other lipid mediators. However, the implication of adipose COX-2 in obesity remains largely unknown. Using adipocyte-specific COX-2 knockout (KO) mice, we showed that depleting COX-2 in adipocytes promoted white adipose tissue development accompanied with increased size and number of adipocytes and predisposed diet-induced adiposity, obesity, and insulin resistance. The increased size and number of adipocytes by COX-2 KO were reversed by the treatment of prostaglandin E2 (PGE2) but not PGI2 and PGD2 during adipocyte differentiation. PGE2 suppresses PPARγ expression through the PKA pathway at the early phase of adipogenesis, and treatment of PGE2 or PKA activator isoproterenol diminished the increased lipid droplets in size and number in COX-2 KO primary adipocytes. Administration of PGE2 attenuated increased fat mass and fat percentage in COX-2 deficient mice. Taken together, our study demonstrated the suppressing effect of adipocyte COX-2 on adipogenesis and reveals that COX-2 restrains adipose tissue expansion via the PGE2-mediated paracrine mechanism and prevents the development of obesity and related metabolic disorders.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Banks, Alexander S.;McAllister, Fiona E.;Camporez, Joao Paulo G.;Zushin, Peter-James H.;Jurczak, Michael J.;Laznik-Bogoslavski, Dina;Shulman, Gerald I.;Gygi, Steven P.;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
DOI：
10.4049/jimmunol.181.8.5646
发表时间：
2008-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jennewein C;Kuhn AM;Schmidt MV;Meilladec-Jullig V;von Knethen A;Gonzalez FJ;Brüne B
通讯作者：
Brüne B
钙敏感受体通过 PPARγ 途径促进脂肪细胞分化和脂肪生成
影响因子：
4.3
作者：
He, Yong-Han;He, Ying;Sun, Chang-Hao
通讯作者：
Sun, Chang-Hao
影响因子：
4.6
作者：
Danneskiold-Samsoe, Niels Banhos;Sonne, Si Brask;Kristiansen, Karsten
通讯作者：
Kristiansen, Karsten