Loss of phospholipase PLAAT3 causes lipodystrophy due to impaired PPAR signaling

PLAAT3 is a phospholipid modifying enzyme predominantly expressed in neural and white adipose tissue (WAT). We identified loss-of-function variants in human PLAAT3 as the cause of a severe lipodystrophy syndrome associated with neurological with features. To identify the underlying molecular pathways associated with PLAAT3 deficiency, we performed RNA sequencing and differential gene expression analysis on WAT specimens from Plaat3 knockout mice. We obtained 15 inguinal WAT samples from 11-week-old mice. Seven Plaat3-/- specimens (3 males, 4 females) were compared to 8 Plaat3+/- littermates (4 males, 4 females) were included.PLAAT3是一种主要在神经系统与白色脂肪组织（white adipose tissue, WAT）中表达的磷脂修饰酶。我们鉴定出人类PLAAT3的功能丧失变异体，是一类伴有神经系统特征的重症脂肪营养不良综合征的致病原因。为探明PLAAT3缺陷相关的潜在分子通路，我们对Plaat3基因敲除小鼠的白色脂肪组织标本开展了RNA测序与差异基因表达分析。我们从11周龄小鼠中采集了15份腹股沟白色脂肪组织样本。本研究纳入7份Plaat3纯合敲除（Plaat3-/-）样本（雄性3只、雌性4只），并以8份Plaat3杂合子（Plaat3+/-）同窝小鼠样本作为对照（雄性4只、雌性4只）。