Defective differentiation of adipose precursor cells from lipodystrophic mice lacking perilipin 1.
Defective differentiation of adipose precursor cells from lipodystrophic mice lacking perilipin 1.
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缺乏 Perilipin 1 的脂肪营养不良小鼠脂肪前体细胞的分化缺陷
DOI：
10.1371/journal.pone.0117536
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Xu G
中科院分区：
文献类型：
--
作者：
Lyu Y;Su X;Deng J;Liu S;Zou L;Zhao X;Wei S;Geng B;Xu G
Perilipin 1(Plin1)定位于脂滴表面，调节脂肪细胞中甘油三酯的储存和水解。Plin1缺陷导致小鼠的低脂肪和人类的部分脂营养不良。本研究探讨了Plin1在脂肪细胞分化中的作用。Plin1基因缺失(-/-)的小鼠在脂肪组织中显示出大量的多房脂肪细胞和小的单眼脂肪细胞，同时缺乏能够在体内成脂的脂肪前体细胞亚群，并伴随着成脂途径的下调。在分化开始前，来自Plin1-/-小鼠的脂肪基质血管细胞(SVCs)已经积累了许多微小的脂滴，在诱导的第一个12小时，这些脂滴的数量和大小增加，但之后在分化的第一天就消失了。尽管PPARγ在Plin1-/-SVCs中的蛋白水平接近正常，但成脂信号转导机制与Plin1/-脂肪组织相似。杂合子Plin1+/-SVCs能够形成脂滴，其数量和大小均大于Plin1-/-SVCs，但少于Plin1+/+SVCs，表明Plin1单倍体不足是脂肪形成减弱的原因。腺病毒Plin1的表达可挽救Plin1-/-SVC的异常脂滴生长和分化，增强或延长成脂刺激可改善Plin1-/-SVC的功能。我们的发现表明，Plin1在脂肪细胞分化中起着重要作用，并为了解Plin1突变患者部分性脂肪营养不良的病理机制提供了线索。
Perilipin 1 (Plin1) localizes at the surface of lipid droplets to regulate triglyceride storage and hydrolysis in adipocytes. Plin1 defect leads to low adiposity in mice and partial lipodystrophy in human. This study investigated the roles of Plin1 in adipocyte differentiation. Plin1 null (-/-) mice showed plenty of multilocular adipocytes and small unilocular adipocytes in adipose tissue, along with lack of a subpopulation of adipose progenitor cells capable of in vivo adipogenesis and along with downregulation of adipogenic pathway. Before initiation of differentiation, adipose stromal-vascular cells (SVCs) from Plin1-/- mice already accumulated numerous tiny lipid droplets, which increased in number and size during the first 12-h induction but thereafter became disappeared at day 1 of differentiation. The adipogenic signaling was dysregulated despite protein level of PPARγ was near normal in Plin1-/- SVCs like in Plin1-/- adipose tissue. Heterozygous Plin1+/- SVCs were able to develop lipid droplets, with both the number and size more than in Plin1-/- SVCs but less than in Plin1+/+ SVCs, indicating that Plin1 haploinsufficiency accounts for attenuated adipogenesis. Aberrant lipid droplet growth and differentiation of Plin1-/- SVCs were rescued by adenoviral Plin1 expression and were ameliorated by enhanced or prolonged adipogenic stimulation. Our finding suggests that Plin1 plays an important role in adipocyte differentiation and provides an insight into the pathology of partial lipodystrophy in patients with Plin1 mutation.
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影响因子：
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作者：
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