Lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis, but not developmental adipogenesis or diet-induced obesity in mice.
Lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis, but not developmental adipogenesis or diet-induced obesity in mice.
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DOI：
10.1371/journal.pone.0198063
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Smyth SS
中科院分区：
文献类型：
--
作者：
Federico L;Yang L;Brandon J;Panchatcharam M;Ren H;Mueller P;Sunkara M;Escalante-Alcalde D;Morris AJ;Smyth SS
磷脂酸（PA）的脱磷酸化是甘油三酯合成的倒数第二步。脂肪细胞表达可溶性细胞内PA特异性磷酸酶（Lipins）和更广泛特异性的膜相关脂质磷酸磷酸酶（LPP），也可以使PA去磷酸化。lipin 1的失活导致小鼠由于发育性脂肪形成缺陷而出现脂肪营养不良。甘油三酯合成减少，但不消融的分化脂肪细胞中的lipin 1的灭活牵连其他PA磷酸酶在这一过程中。为了研究LPPs在脂肪细胞脂质代谢和信号传导中的可能作用，我们用脂肪细胞靶向失活由Plpp 3（Ppap 2b）基因编码的LPP 3制备小鼠。脂肪细胞LPP 3缺乏导致在饮食诱导的脂肪组织扩张过程中神经酰胺和鞘磷脂的积累钝化，LPP 3底物鞘氨醇1-磷酸的积累，丝氨酸棕榈酰转移酶的表达减少。然而，在标准、高脂肪饮食或西方饮食中，肥胖不受LPP 3缺乏的影响，尽管西方饮食喂养的脂肪细胞LPP 3缺乏的小鼠表现出改善的葡萄糖耐量。我们的研究结果表明脂肪细胞中脂质磷酸酶活性的功能区室化，并确定了LPP 3在调节饮食依赖性鞘脂合成中的意想不到的作用，这可能会影响胰岛素信号传导。
Dephosphorylation of phosphatidic acid (PA) is the penultimate step in triglyceride synthesis. Adipocytes express soluble intracellular PA-specific phosphatases (Lipins) and broader specificity membrane-associated lipid phosphate phosphatases (LPPs) that can also dephosphorylate PA. Inactivation of lipin1 causes lipodystrophy in mice due to defective developmental adipogenesis. Triglyceride synthesis is diminished but not ablated by inactivation of lipin1 in differentiated adipocytes implicating other PA phosphatases in this process. To investigate the possible role of LPPs in adipocyte lipid metabolism and signaling we made mice with adipocyte-targeted inactivation of LPP3 encoded by the Plpp3(Ppap2b) gene. Adipocyte LPP3 deficiency resulted in blunted ceramide and sphingomyelin accumulation during diet-induced adipose tissue expansion, accumulation of the LPP3 substrate sphingosine 1- phosphate, and reduced expression of serine palmitoyl transferase. However, adiposity was unaffected by LPP3 deficiency on standard, high fat diet or Western diets, although Western diet-fed mice with adipocyte LPP3 deficiency exhibited improved glucose tolerance. Our results demonstrate functional compartmentalization of lipid phosphatase activity in adipocytes and identify an unexpected role for LPP3 in the regulation of diet-dependent sphingolipid synthesis that may impact on insulin signaling.
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影响因子：
1.2
作者：
Ile, Kristina E.;Renault, Andrew D.
通讯作者：
Renault, Andrew D.
在LDLR - / - 小鼠中，分泌性鞘磷脂酶活性，脂蛋白鞘脂含量和LDL聚集的表征。
影响因子：
4
作者：
Deevska GM;Sunkara M;Morris AJ;Nikolova-Karakashian MN
通讯作者：
Nikolova-Karakashian MN
DOI：
10.1161/atvbaha.112.300527
发表时间：
2013-01
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Panchatcharam M;Miriyala S;Salous A;Wheeler J;Dong A;Mueller P;Sunkara M;Escalante-Alcalde D;Morris AJ;Smyth SS
通讯作者：
Smyth SS
影响因子：
5.3
作者：
Kang, S;Bajnok, L;MacDougald, OA
通讯作者：
MacDougald, OA
影响因子：
1.5
作者：
Escalante-Alcalde, Diana;Sanchez-Sanchez, Roberto;Stewart, Colin L.
通讯作者：
Stewart, Colin L.