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

Sci Rep. 2018 Mar 21;8(1):4974. doi: 10.1038/s41598-018-23267-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acclimatization / physiology*
  • Adipocytes, Beige / physiology*
  • Adipocytes, Brown / metabolism*
  • Adipogenesis / physiology*
  • Animals
  • Bone Marrow Cells / physiology
  • Cell Differentiation
  • Cell Line
  • Cold Temperature / adverse effects*
  • Mesenchymal Stem Cells / physiology
  • Mice
  • Thermogenesis / physiology
  • Uncoupling Protein 1 / metabolism
  • Up-Regulation

Substances

  • Ucp1 protein, mouse
  • Uncoupling Protein 1