Abstract
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(2) 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(3) -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(2+) release which results in elevated O(2) 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.