Somatic cell plasticity and Niemann-pick type C2 protein: adipocyte differentiation and function.

The Journal of Biological Chemistry
Chad CsepeggiAndrey Frolov

Abstract

The phenotypic stability of somatic cells is essential for the maintenance of both structural and functional organ integrity of the adult human body. Deregulated cell plasticity could result in the development of debilitating diseases such as cancer, fibrosis, atherosclerosis, obesity, and type 2 diabetes. We have previously demonstrated that a nonsense mutation in the NPC2 gene, which encodes ubiquitous, highly conserved, secretory protein with unknown function, leads to activation of human skin fibroblasts. The activated fibroblasts, also known as myofibroblasts, have the properties of mesenchymal stem cells and are able to differentiate along the mesodermal and endodermal lineages. Here we show that NPC2-null, but not the normal skin fibroblasts, possess characteristics of adipogenic progenitors as demonstrated by their specific gene expression pattern as well as the ability for efficient differentiation into white adipocytes. The presence of NPC2 in mature white adipocytes was also necessary for their maintenance because silencing NPC2 in differentiated cells by siRNA stimulated PPARG expression, which was followed by a shift toward a more favorable, brown adipocyte-like metabolic state characterized by up-regulated lipolys...Continue Reading

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Citations

Nov 19, 2010·The Journal of Biological Chemistry·Chad CsepeggiAndrey Frolov
Dec 4, 2012·International Journal of Molecular Sciences·Andrés García-LorenzoVicenta S Martínez-Zorzano
Apr 7, 2015·Drug Discoveries & Therapeutics·Tatsuo AdachiKazuhisa Sekimizu
Mar 10, 2018·PloS One·Claus Uhrenholt ChristensenHenning Grønbæk
Dec 2, 2020·International Journal of Molecular Sciences·Valentina Pallottini, Frank W Pfrieger

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