title: Stress hormone epinephrine enhances adipogenesis in murine embryonic stem cells by up-regulating the neuropeptide Y system.
abstract: Prenatal stress, psychologically and metabolically, increases the risk of obesity and diabetes in the progeny. However, the mechanisms of the pathogenesis remain unknown. In adult mice, stress activates NPY and its Y2R in a glucocorticoid-dependent manner in the abdominal fat. This increased adipogenesis and angiogenesis, leading to abdominal obesity and metabolic syndrome which were inhibited by intra-fat Y2R inactivation. To determine whether stress elevates NPY system and accelerates adipogenic potential of embryo, here we "stressed" murine embryonic stem cells (mESCs) in vitro with epinephrine (EPI) during their adipogenic differentiation. EPI was added during the commitment stage together with insulin, and followed by dexamethasone in the standard adipogenic differentiation medium. Undifferentiated embryonic bodies (EBs) showed no detectable expression of NPY. EPI markedly up-regulated the expression NPY and the Y1R at the commitment stage, followed by increased Y2R mRNA at the late of the commitment stage and the differentiation stage. EPI significantly increased EB cells proliferation and expression of the preadipocyte marker Pref-1 at the commitment stage. EPI also accelerated and amplified adipogenic differentiation detected by increasing the adipocyte markers FABP4 and PPARγ mRNAs and Oil-red O-staining at the end of the differentiation stage. EPI-induced adipogenesis was completely prevented by antagonists of the NPY receptors (Y1R+Y2R+Y5R), indicating that it was mediated by the NPY system in mESC's. Taken together, these data suggest that stress may play an important role in programming ESCs for accelerated adipogenesis by altering the stress induced hormonal regulation of the NPY system.
authors.affiliation: Department of Integrative Biology and Physiology, Stress Physiology Center, University of Minnesota, Minneapolis, Minnesota, USA. rhan@umn.edu
authors.forename: Ruijun
authors.initials: R
authors.lastname: Han
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Kitlinska
authors.forename: William R
authors.initials: WR
authors.lastname: Munday
authors.forename: G Ian
authors.initials: GI
authors.lastname: Gallicano
authors.forename: Zofia
authors.initials: Z
authors.lastname: Zukowska
mesh_terms: D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D009478:Neuropeptide Y / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000235:genetics* / Q000378:metabolism; D013312:Stress, Physiological; D015854:Up-Regulation
chemical_list: D007328:Insulin; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D004837:Epinephrine