Low temperature exposure induces browning of bone marrow stem cell derived adipocytes in vitro

Brown and beige adipocytes are characterised as expressing the unique mitochondrial uncoupling protein (UCP)1 for which the primary stimulus in vivo is cold exposure. The extent to which cold-induced UCP1 activation can also be achieved in vitro, and therefore perform a comparable cellular function,...

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Main Authors: Velickovic, Ksenija, Lugo-Leija, Hilda Anaid, Bloor, Ian, Law, James, Sacks, Harold, Symonds, Michael E., Sottile, Virginie
Format: Article
Language:English
Published: Nature Publishing Group 2018
Online Access:https://eprints.nottingham.ac.uk/50341/
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author Velickovic, Ksenija
Lugo-Leija, Hilda Anaid
Bloor, Ian
Law, James
Sacks, Harold
Symonds, Michael E.
Sottile, Virginie
author_facet Velickovic, Ksenija
Lugo-Leija, Hilda Anaid
Bloor, Ian
Law, James
Sacks, Harold
Symonds, Michael E.
Sottile, Virginie
author_sort Velickovic, Ksenija
building Nottingham Research Data Repository
collection Online Access
description Brown and beige adipocytes are characterised as expressing the unique mitochondrial uncoupling protein (UCP)1 for which the primary stimulus in vivo is cold exposure. The extent to which cold-induced UCP1 activation can also be achieved in vitro, and therefore perform a comparable cellular function, is unknown. We report an in vitro model to induce adipocyte browning using bone marrow (BM) derived mesenchymal stem cells (MSC), which relies on differentiation at 32°C instead of 37°C. The low temperature promoted browning in adipogenic cultures, with increased adipocyte differentiation and upregulation of adipogenic and thermogenic factors, especially UCP1. Cells exhibited enhanced uncoupled respiration and metabolic adaptation. Cold-exposed differentiated cells showed a marked translocation of leptin to adipocyte nuclei, suggesting a previously unknown role for leptin in the browning process. These results indicate that BM-MSC can be driven to forming beige-like adipocytes in vitro by exposure to a reduced temperature. This in vitro model will provide a powerful tool to elucidate the precise role of leptin and related hormones in hitherto functions in the browning process.
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spelling nottingham-503412018-08-10T10:49:47Z https://eprints.nottingham.ac.uk/50341/ Low temperature exposure induces browning of bone marrow stem cell derived adipocytes in vitro Velickovic, Ksenija Lugo-Leija, Hilda Anaid Bloor, Ian Law, James Sacks, Harold Symonds, Michael E. Sottile, Virginie Brown and beige adipocytes are characterised as expressing the unique mitochondrial uncoupling protein (UCP)1 for which the primary stimulus in vivo is cold exposure. The extent to which cold-induced UCP1 activation can also be achieved in vitro, and therefore perform a comparable cellular function, is unknown. We report an in vitro model to induce adipocyte browning using bone marrow (BM) derived mesenchymal stem cells (MSC), which relies on differentiation at 32°C instead of 37°C. The low temperature promoted browning in adipogenic cultures, with increased adipocyte differentiation and upregulation of adipogenic and thermogenic factors, especially UCP1. Cells exhibited enhanced uncoupled respiration and metabolic adaptation. Cold-exposed differentiated cells showed a marked translocation of leptin to adipocyte nuclei, suggesting a previously unknown role for leptin in the browning process. These results indicate that BM-MSC can be driven to forming beige-like adipocytes in vitro by exposure to a reduced temperature. This in vitro model will provide a powerful tool to elucidate the precise role of leptin and related hormones in hitherto functions in the browning process. Nature Publishing Group 2018-03-21 Article PeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/50341/13/s41598-018-23267-9.pdf Velickovic, Ksenija, Lugo-Leija, Hilda Anaid, Bloor, Ian, Law, James, Sacks, Harold, Symonds, Michael E. and Sottile, Virginie (2018) Low temperature exposure induces browning of bone marrow stem cell derived adipocytes in vitro. Scientific Reports, 8 . 4974/1-4674/12. ISSN 2045-2322 https://www.nature.com/articles/s41598-018-23267-9 doi:10.1038/s41598-018-23267-9 doi:10.1038/s41598-018-23267-9
spellingShingle Velickovic, Ksenija
Lugo-Leija, Hilda Anaid
Bloor, Ian
Law, James
Sacks, Harold
Symonds, Michael E.
Sottile, Virginie
Low temperature exposure induces browning of bone marrow stem cell derived adipocytes in vitro
title Low temperature exposure induces browning of bone marrow stem cell derived adipocytes in vitro
title_full Low temperature exposure induces browning of bone marrow stem cell derived adipocytes in vitro
title_fullStr Low temperature exposure induces browning of bone marrow stem cell derived adipocytes in vitro
title_full_unstemmed Low temperature exposure induces browning of bone marrow stem cell derived adipocytes in vitro
title_short Low temperature exposure induces browning of bone marrow stem cell derived adipocytes in vitro
title_sort low temperature exposure induces browning of bone marrow stem cell derived adipocytes in vitro
url https://eprints.nottingham.ac.uk/50341/
https://eprints.nottingham.ac.uk/50341/
https://eprints.nottingham.ac.uk/50341/