ADRB3

The beta-3 adrenergic receptor (β3-AR) is a cell surface G-protein coupled receptor (GPCR) that plays a crucial role in regulating energy homeostasis, lipid metabolism, and thermogenesis. It is one of the three known beta-adrenergic receptor subtypes (β1-AR, β2-AR, and β3-AR), which mediate the effects of catecholamines, such as adrenaline and noradrenaline, on various physiological processes.

β3-AR is predominantly expressed in adipose tissue, particularly in brown and white adipocytes, as well as in the urinary bladder and the gastrointestinal tract. In adipose tissue, activation of β3-AR by its ligands leads to the stimulation of adenylate cyclase, which in turn increases intracellular cyclic AMP (cAMP) levels. Elevated cAMP activates protein kinase A (PKA), which then phosphorylates various downstream targets, ultimately promoting lipolysis and thermogenesis.

In brown adipose tissue (BAT), β3-AR activation enhances the breakdown of triglycerides into free fatty acids, which are subsequently oxidized to generate heat through a process known as non-shivering thermogenesis. This process is mediated by the mitochondrial uncoupling protein 1 (UCP1), which dissipates the proton gradient across the inner mitochondrial membrane, converting chemical energy into heat. In white adipose tissue (WAT), β3-AR activation stimulates lipolysis and may promote the "browning" of white adipocytes, increasing their thermogenic capacity.

The β3-AR has been identified as a potential therapeutic target for obesity and related metabolic disorders. Pharmacological activation of β3-AR has been shown to increase energy expenditure, reduce adiposity, and improve insulin sensitivity in animal models. However, the development of selective β3-AR agonists for human use has been challenging due to species differences in receptor pharmacology and function. Further research is needed to fully understand the therapeutic potential of targeting β3-AR in the treatment of obesity and metabolic diseases.

In summary, the beta-3 adrenergic receptor (β3-AR) is a GPCR involved in the regulation of energy homeostasis, lipid metabolism, and thermogenesis, primarily through its expression in adipose tissue. Activation of β3-AR promotes lipolysis and thermogenesis, making it an attractive target for the development of novel therapeutics aimed at treating obesity and related metabolic disorders.