Stem Cell‐Based Modelling of Brown Adipogenesis Using Hypothermal Conditions

Abstract

In vivo cold exposure is the main stimulus to activate the unique mitochondrial uncoupling protein (UCP)1, known for mediating heat production in brown and beige adipocytes. In vitro, UCP1 adipogenic response under hypothermic conditions requires an extended evaluation in order to be comparable to an in vivo cellular function. We have developed a new in vitro culture system to induce adipogenic browning in bone marrow (BM) derived mesenchymal stem cells (MSC), using exposure to reduced temperature during differentiation. Incubation at 32°C instead of 37°C over the course of the culture treatment was seen to promote brown adipogenesis with increased adipocyte response and upregulation of adipogenic and thermogenic factors including UCP1. Adipocytes differentiated under hypothermic conditions displayed enhanced uncoupled respiration and metabolic adaptation, as well as significant durable changes in cellular and molecular features. These results suggest that MSC available from accessible tissue sources can be differentiated in vitro using cold temperature conditions to favor the appearance of functional beige‐like adipocytes. This cell‐based model represents a new valuable tool to screen for pro‐browning factors in vitro and elucidate the mechanism of metabolic adaptation relevant to the browning process.Support or Funding InformationThis work was funded by the EU‐CASCADE fellowship scheme funded by the EU's 7th FP PCOFUND‐GA‐2012‐600181 (K.V.), CONACyT, Mexico (H.A.L.L.), and received support from The Cardiometabolic Disease Research Foundation (Los Angeles, USA) and the Biotechnology and Biological Sciences Research Council (BBSRC, Multidisciplinary Super Resolution Microscopy Facility grant BB/L013827/1).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.