The lipase cofactor CGI58 controls placental lipolysis.
The lipase cofactor CGI58 controls placental lipolysis.
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DOI：
10.1172/jci.insight.168717
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发表时间：
2023-05-22
期刊：
影响因子：
8
通讯作者：
Sadovsky, Yoel
中科院分区：
文献类型：
--
作者：
Guerrero-Santoro, Jennifer;Morizane, Mayumi;Oh, Soo-Young;Mishima, Takuya;Goff, Julie P.;Bildirici, Ibrahim;Sadovsky, Elena;Ouyang, Yingshi;Tyurin, Vladimir A.;Tyurina, Yulia Y.;Kagan, Valerian E.;Sadovsky, Yoel
在真兽目动物中，胎盘在脂质的摄取、储存和代谢中起着关键作用。这些过程控制着脂肪酸对发育中的胎儿的可用性，其中供应不足与胎儿生长不达标有关。尽管脂滴对于胎盘和许多其他组织中中性脂质的储存是必不可少的，但调节胎盘脂滴脂解的过程在很大程度上仍然未知。为了评估甘油三酯脂肪酶及其辅因子在决定胎盘脂滴和脂质蓄积中的作用，我们评估了马铃薯糖蛋白样磷脂酶结构域2（PNPLA 2）和比较基因识别-58（CGI 58）在人类和小鼠胎盘脂滴动力学中的作用。虽然这两种蛋白质都在胎盘中表达，但缺乏CGI 58而不是PNPLA 2显著增加了胎盘脂质和脂滴积累。这些变化在CGI 58缺陷小鼠胎盘中选择性地恢复CGI 58水平后被逆转。使用免疫共沉淀，我们发现，除了PNPLA 2，PNPLA 9与CGI 58相互作用。PNPLA 9在小鼠胎盘中被证实为脂解，但在人胎盘滋养层中促进脂解。我们的研究结果确立了CGI 58在胎盘脂滴动力学中的关键作用，并延伸到发育中胎儿的营养供应。
In eutherians, the placenta plays a critical role in the uptake, storage, and metabolism of lipids. These processes govern the availability of fatty acids to the developing fetus, where inadequate supply has been associated with substandard fetal growth. Whereas lipid droplets are essential for the storage of neutral lipids in the placenta and many other tissues, the processes that regulate placental lipid droplet lipolysis remain largely unknown. To assess the role of triglyceride lipases and their cofactors in determining placental lipid droplet and lipid accumulation, we assessed the role of patatin like phospholipase domain containing 2 (PNPLA2) and comparative gene identification-58 (CGI58) in lipid droplet dynamics in the human and mouse placenta. While both proteins are expressed in the placenta, the absence of CGI58, not PNPLA2, markedly increased placental lipid and lipid droplet accumulation. These changes were reversed upon restoration of CGI58 levels selectively in the CGI58-deficient mouse placenta. Using co-immunoprecipitation, we found that, in addition to PNPLA2, PNPLA9 interacts with CGI58. PNPLA9 was dispensable for lipolysis in the mouse placenta yet contributed to lipolysis in human placental trophoblasts. Our findings establish a crucial role for CGI58 in placental lipid droplet dynamics and, by extension, in nutrient supply to the developing fetus.
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DOI：
10.1074/jbc.m115.682203
发表时间：
2015-10-30
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Boeszoermenyi A;Nagy HM;Arthanari H;Pillip CJ;Lindermuth H;Luna RE;Wagner G;Zechner R;Zangger K;Oberer M
通讯作者：
Oberer M
影响因子：
4.8
作者：
Eichmann, Thomas O.;Kumari, Manju;Zechner, Rudolf
通讯作者：
Zechner, Rudolf
影响因子：
4.3
作者：
Campbell, FM;Gordon, MJ;DuttaRoy, AK
通讯作者：
DuttaRoy, AK
DOI：
10.1073/pnas.2009201117
发表时间：
2020-11-03
影响因子：
11.1
作者：
Beharier, Ofer;Tyurin, Vladimir A.;Sadovsky, Yoel
通讯作者：
Sadovsky, Yoel
影响因子：
3.7
作者：
Barrett HL;Kubala MH;Scholz Romero K;Denny KJ;Woodruff TM;McIntyre HD;Callaway LK;Nitert MD
通讯作者：
Nitert MD