Cold-induced beigeing of stem cell-derived adipocytes is not fully reversible after return to normothermia

Lugo Leija, Hilda Anaid; Velickovic, Ksenija; Bloor, Ian; Sacks, Harold; Symonds, Michael E.; Sottile, Virginie

Abstract

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 (i.e. 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 (e.g. 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 acclimatisation at 37°C, indicating these phenotypic characteristics acquired in response to environmental conditions are not fully reversible.

Citation

Lugo Leija, H. A., Velickovic, K., Bloor, I., Sacks, H., Symonds, M. E., & Sottile, V. (2020). Cold-induced beigeing of stem cell-derived adipocytes is not fully reversible after return to normothermia. Journal of Cellular and Molecular Medicine, 24(19), 11434-11444. https://doi.org/10.1111/jcmm.15749

• Journal Article Type: Article
• Acceptance Date: Jul 30, 2020
• Online Publication Date: Sep 9, 2020
• Publication Date: Sep 9, 2020
• Deposit Date: Aug 5, 2020
• Publicly Available Date: Sep 9, 2020
• Journal: Journal of Cellular and Molecular Medicine
• Print ISSN: 1582-1838
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 24
• Issue: 19
• Pages: 11434-11444
• DOI: https://doi.org/10.1111/jcmm.15749
• Keywords: Stem cell, Adipogenesis, Brown adipose tissue, Differentiation, Temperature
• Public URL: https://nottingham-repository.worktribe.com/output/4812109
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.15749