Optogenetic activation of UCP1-dependent thermogenesis in brown adipocytes

Chad C Doucette; Daniel C Nguyen; Davide Barteselli; Sophia Blanchard; Mason Pelletier; Devesh Kesharwani; Ed Jachimowicz; Su Su; Michele Karolak; Aaron C Brown

doi:10.1016/j.isci.2023.106560

Optogenetic activation of UCP1-dependent thermogenesis in brown adipocytes

iScience. 2023 Apr 1;26(4):106560. doi: 10.1016/j.isci.2023.106560. eCollection 2023 Apr 21.

Authors

Affiliations

¹ MaineHealth Institute for Research, 81 Research Drive, Scarborough, ME 04074, USA.
² School of Biomedical Sciences and Engineering, University of Maine, Orono, ME 04469, USA.
³ Tufts University School of Medicine, 145 Harrison Avenue, Boston, MA 02111, USA.

Abstract

Brown adipocytes are unique in that they expend energy and produce heat to maintain euthermia through expression of uncoupling protein-1 (UCP1). Given their propensity to stimulate weight loss and promote resistance to obesity, they are a compelling interventional target for obesity-related disorders. Here, we tested whether an optogenetic approach could be used to activate UCP1-dependent thermogenesis in brown adipocytes. We generated brown adipocytes expressing a bacterial-derived photoactivatable adenylyl cyclase (bPAC) that, upon blue light stimulation, increases UCP1 expression, fuel uptake and thermogenesis. This unique system allows for precise, chemical free, temporal control of UCP1-dependent thermogenesis, which can aid in our understanding of brown adipocyte biology and development of therapies that target obesity-related disorders.

Keywords: Metabolic engineering; Molecular biology experimental approach; Specialized functions of cells.