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Exposure to a reduced ambient temperature induces browning of bone marrow derived adipocytes in vitro
Author(s) -
Symonds Michael,
Velickovic K,
LugoLeija H A.,
Bloor Ian,
Law James,
Sacks H,
Sottile Virginie
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.615.12
Subject(s) - adipogenesis , microbiology and biotechnology , lipid droplet , adipocyte , browning , bioenergetics , chemistry , thermogenin , mesenchymal stem cell , downregulation and upregulation , thermogenesis , adipose tissue , mitochondrion , endocrinology , medicine , biology , biochemistry , gene
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 ability to promote the abundance of UCP1 can have a beneficial effect on energy balance as well as lipid and carbohydrate metabolism and as such is a potential anti‐diabesity target. This process has not been studied widely in vitro, for which the impact of modulation of the thermal environment is not well established. The aim of our study was therefore to examine whether cold‐induced UCP1 activation can be achieved in vitro. We thus report an in vitro model to induce adipocyte browning using bone marrow (BM) derived mesenchymal stem cells (MSC) of both human and mouse origin. It relies on differentiation at a cool ambient temperature of 32°C instead of the standard temperature of 37°C. The low temperature promoted browning in MSC‐derived adipogenic cultures, with increased adipocyte number (including multilocular cells), and upregulation of adipogenic and thermogenic factors, especially UCP1. Lipid droplets were smaller and more numerous. The bioenergetic status of cells was then investigated using a Seahorse XF96 flux analyser, and the overall respiratory responses calculated for the six key regulators of mitochondrial function. Cells differentiated at 32°C exhibited enhanced uncoupled respiration and metabolic adaptation, with intensified oxidative and glycolytic pathways. Cold‐exposed differentiated cells showed a marked translocation of regulatory hormones to adipocyte nuclei, suggesting a previously unknown role in the browning process. To further determine whether this adipogenic phenotype acquired at 32°C may be reversible as found in vivo, cells differentiated at 32°C were subsequently transferred to standard culture conditions (37°C). This showed that cells transferred from 32°C to 37°C showed a pattern of UCP1 expression similar to that of cells differentiated at 32°C i.e. they retained their beige‐like characteristics. Taken together 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 now provide a powerful tool to further elucidate the regulation of UCP1 function in order to provide a better understanding of the endocrine regulation of the browning process in human adipocytes. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .