Elucidation of the roles of brown and brite fat genes: GPR120 is a modulator of brown adipose tissue function.

New Findings: What is the topic of this review? Activation of brown adipose tissue with G protein-coupled receptors as key druggable targets as a strategy to increase energy consumption and reduce fat mass. What advances does it highlight? GPR120 is a fatty acid receptor highly expressed in brown adipose tissue. Its activation by selective ligands increases brown adipose tissue activity. This is mediated by changes in mitochondrial dynamics resulting in increased O consumption leading to enhanced nutrient uptake and a reduction in fat mass.

Abstract: The identification of druggable targets to stimulate brown adipose tissue (BAT) is a strategy to combat obesity due to this highly metabolically active tissue utilising thermogenesis to burn fat. Upon cold exposure BAT is activated by the sympathetic nervous system via β -adrenergic receptors. Determination of additional receptors expressed by brown, white and brite (brown-in-white) fat can lead to new pharmacological treatments to activate BAT. GPR120 is a G protein-coupled fatty acid receptor that is highly expressed in BAT and further increases in response to cold. Activation of this receptor with the selective agonist TUG-891 acutely increases fat oxidation and reduces fat mass in mice. The effects are coincident with increased BAT activity and enhanced nutrient uptake. TUG-891 stimulation of brown adipocytes induces intracellular Ca release which results in elevated O consumption as well as mitochondrial depolarisation and fission. Thus, activation of GPR120 in BAT with ligands such as TUG-891 is a promising strategy to increase fat consumption.