Pathological analysis of Prader-Willi syndrome using adipocytes.

Prader-Willi syndrome (PWS) is a complex epigenetic disorder caused by the deficiency of paternally expressed genes in chromosome 15q11-q13. This syndrome also includes endocrine dysfunction, leading to short stature, hypogonadism, and obscure hyperphagia. Although recent progress has been made toward understanding the genetic basis for PWS, the molecular mechanisms underlying its pathology in obesity remain unclear. In this study, we examined the adipocytic characteristics of two PWS-induced pluripotent stem cell (iPSC) lines: those with the 15q11-q13 gene deletion (iPWS cells) and those with 15q11-q13 abnormal methylation (M-iPWS cells). The transcript levels of the lipid-binding protein aP2 were decreased in iPWS and M-iPWS adipocytes. Flow-cytometry analysis showed that PWS adipocytes accumulated more lipid droplets than did normal individual adipocytes. Furthermore, glucose uptake upon insulin stimulation was attenuated compared to that in normal adipocytes. Overall, our results suggest a significantly increased lipid content and defective in glucose metabolism in PWS adipocytes.