Cold-induced beigeing of stem cell-derived adipocytes is not fully reversible after return to normothermia.
Beige adipocytes possess the morphological and biochemical characteristics of brown adipocytes, including the mitochondrial uncoupling protein (UCP)1. Mesenchymal stem cells (MSCs) are somatic multipotent progenitors which differentiate into lipid-laden adipocytes. Induction of MSC adipogenesis under hypothermic culture conditions (ie 32°C) promotes the appearance of a beige adipogenic phenotype, but the stability of this phenotypic switch after cells are returned to normothermic conditions of 37°C has not been fully examined. Here, cells transferred from 32°C to 37°C retained their multilocular beige-like morphology and exhibited an intermediate gene expression profile, with both beige-like and white adipocyte characteristics while maintaining UCP1 protein expression. Metabolic profile analysis indicated that the bioenergetic status of cells initially differentiated at 32°C adapted post-transfer to 37°C, showing an increase in mitochondrial respiration and glycolysis. The ability of the transferred cells to respond under stress conditions (eg carbonyl cyanide-4-phenylhydrazone (FCCP) treatment) demonstrated higher functional capacity of enzymes involved in the electron transport chain and capability to supply substrate to the mitochondria. Overall, MSC-derived adipocytes incubated at 32°C were able to remain metabolically active and retain brown-like features after 3 weeks of acclimatization at 37°C, indicating these phenotypic characteristics acquired in response to environmental conditions are not fully reversible.
['Lugo Leija|Hilda Anaid|HA|', 'Velickovic|Ksenija|K|', 'Bloor|Ian|I|', 'Sacks|Harold|H|', 'Symonds|Michael E|ME|0000-0001-9649-8963', 'Sottile|Virginie|V|0000-0002-6064-5738']
D000069797:Adipocytes, Beige D052437:Adipocytes, Brown D050156:Adipogenesis D000818:Animals D015415:Biomarkers D048430:Cell Shape D003080:Cold Temperature D005786:Gene Expression Regulation D059630:Mesenchymal Stem Cells D051379:Mice D008928:Mitochondria D013234:Stem Cells D050916:TRPV Cation Channels D000071256:Uncoupling Protein 1
stem cell differentiation adipogenesis brown adipose tissue temperature