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.