Abstract
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.
Highlights
Two types of adipose tissue are recognized in mammals: white adipose tissue (WAT) and brown adipose tissue (BAT)[1]
More complex roles have been attributed to Bone Marrow (BM) adipocytes, as a passive fat depot, and as cells actively participating in BM lipid metabolism and osteogenesis[22], with features described as a mix of both WAT and BAT characteristics[23]
In order to examine the time course of Mesenchymal stem cells (mMSCs) differentiation, cells were treated with adipogenic medium at 37 °C
Summary
Two types of adipose tissue are recognized in mammals: white adipose tissue (WAT) and brown adipose tissue (BAT)[1]. The most potent physiological stimulus to activate UCP1 is cold exposure, which has been shown to promote the appearance of UCP1 both in vivo and in vitro[4,5] It is unclear, whether this thermal response could have a comparable impact on the regulation of stem cell differentiation into adipocytes. When fully stimulated, beige adipocytes undergo UCP1-mediated respiration[10], but their molecular and developmental characteristics are different from brown adipocytes. We evaluated the potential of BM-derived mouse MSCs to undergo browning and the extent to which this can be modulated by the temperature at which the cells are incubated during differentiation, together with its potential impact on brown/beige markers and leptin expression
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