Palmitate enhances the differentiation of mouse embryonic stem cells towards white adipocyte lineages

The number of adipocyte progenitors is determined early in foetal and neonatal development in a process which may be altered by gender and excess nutrient intake, and which in turn determines fat mass in adulthood and the risk of developing obesity. Here we investigate the hypothesis that excess nutrients, in this case the long chain fatty acid palmitate, can program differentiating stem cells towards white fat lineages. The experiments were performed on mouse embryonic stem cells in chemically defined media (CDM) supplemented with bone morphogenetic protein 4 (BMP4) and all trans-retinoic acid (RA). Subsequent treatment for 21 days with palmitate not only promoted the expression of adipocyte markers and monolocular lipid deposition as observed by RT/QPCR and immunocytochemistry, but also stimulated a considerable enrichment in adipocytes as measured by flow cytometry and a lipolytic response to catecholamines. Palmitate increased protein levels of adiponectin that is preferentially expressed in subcutaneous fat, while inhibiting IGFBP2 and IGFBP3 that are associated with visceral fat. In keeping with this finding, palmitate also increased expression of the subcutaneous markers Shox2 and Twist1 and oestrogenising enzymes. Collectively, these results suggest that palmitate induces differentiation towards subcutaneous fat and that this could occur through its oestrogenising effects on the preadipocyte, suggesting a role for palmitate in programming fat development towards a metabolically favourable profile.