Lipocalin 2 Deficiency Alters Prostaglandin Biosynthesis and mTOR Signaling Regulation of Thermogenesis and Lipid Metabolism in Adipocytes.
Lipocalin 2 Deficiency Alters Prostaglandin Biosynthesis and mTOR Signaling Regulation of Thermogenesis and Lipid Metabolism in Adipocytes.
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Lipocalin 2缺乏改变前列腺素生物合成和脂肪细胞产热和脂质代谢的mTOR信号调节。
DOI：
10.3390/cells11091535
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发表时间：
2022-05-03
期刊：
影响因子：
6
通讯作者：
Chen, Xiaoli
中科院分区：
文献类型：
--
作者：
Deis, Jessica;Lin, Te-Yueh;Bushman, Theresa;Chen, Xiaoli
除了在先天免疫系统中的众所周知的作用之外，脂质运载蛋白2（Lcn 2）最近被表征为产热和脂质代谢的关键调节剂。然而，Lcn 2通过其调节脂肪细胞中的细胞代谢和产热的生理机制仍然未知。我们发现，Lcn 2的表达和分泌显着上调花生四烯酸（AA）和mTORC 1抑制分化的腹股沟脂肪细胞。AA诱导的Lcn 2表达和分泌与炎性NF κ B活化相关。Lcn 2缺陷导致脂肪细胞中环氧合酶-2（COX 2）表达上调，以及AA诱导的前列腺素（PGs），特别是PGE 2和PGD 2的生物合成和分泌增加。此外，Lcn 2缺陷影响产热基因表达、脂肪生成和脂解的mTOR信号转导调节。Lcn 2的缺失消除了雷帕霉素对COX 2、产热基因、脂肪生成和脂解的mTORC 1抑制作用，但对Lcn 2缺陷型脂肪细胞中的p70 S6激酶-ULK 1活化没有影响。我们的结论是，Lcn 2收敛的COX 2-PGE 2和mTOR信号通路在脂肪细胞的产热和脂质代谢的调节。
Apart from a well-known role in the innate immune system, lipocalin 2 (Lcn2) has been recently characterized as a critical regulator of thermogenesis and lipid metabolism. However, the physiological mechanism through which Lcn2 regulates cellular metabolism and thermogenesis in adipocytes remains unknown. We found that Lcn2 expression and secretion are significantly upregulated by arachidonic acid (AA) and mTORC1 inhibition in differentiated inguinal adipocytes. AA-induced Lcn2 expression and secretion correlate with the inflammatory NFkB activation. Lcn2 deficiency leads to the upregulation of cyclooxygenase-2 (COX2) expression, as well as increased biosynthesis and secretion of prostaglandins (PGs), particularly PGE2 and PGD2, induced by AA in adipocytes. Furthermore, Lcn2 deficiency affects the mTOR signaling regulation of thermogenic gene expression, lipogenesis, and lipolysis. The loss of Lcn2 dismisses the effect of mTORC1 inhibition by rapamycin on COX2, thermogenesis genes, lipogenesis, and lipolysis, but has no impact on p70 S6Kinase-ULK1 activation in Lcn2-deficient adipocytes. We conclude that Lcn2 converges the COX2-PGE2 and mTOR signaling pathways in the regulation of thermogenesis and lipid metabolism in adipocytes.
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影响因子：
3.5
作者：
Deis JA;Guo H;Wu Y;Liu C;Bernlohr DA;Chen X
通讯作者：
Chen X
影响因子：
7.7
作者：
Guo H;Jin D;Zhang Y;Wright W;Bazuine M;Brockman DA;Bernlohr DA;Chen X
通讯作者：
Chen X
DOI：
10.1073/pnas.0510847103
发表时间：
2006-02-07
影响因子：
11.1
作者：
Berger, T;Togawa, A;Mak, TW
通讯作者：
Mak, TW
影响因子：
16
作者：
Goetz, DH;Holmes, MA;Strong, RK
通讯作者：
Strong, RK
影响因子：
4.8
作者：
Chen, Sisi;Mei, Xiaohan;Chen, Shi-You
通讯作者：
Chen, Shi-You