BAT thermogenesis is triggered by the release of norepinephrine from the sympathetic nerve terminals which stimulates β3-adrenergic receptors, turning on a cascade of intracellular events including production of UCP1, a protein involved in thermogenesis. TRPV2-mediated calcium influx could regulate the thermogenic gene expression. At room temperature, the sympathetic nerve activity is kept in a resting condition and UCP1 expression level is low which causes less heat production. On the other hand, when cold temperature is detected by peripheral temperature-sensitive nerve endings, sympathetic nervous system could be activated, which leads to norepinephrine release from the sympathetic nerves and activation of β3-adrenergic receptors. Subsequently, TRPV2 expression is up-regulated and more calcium is influxed via TRPV2, facilitating UCP1 expression and heat production.
BAT: brown adipose tissue; FFA: free fatty acids; SNS: sympathetic nervous system; β3ADR: β3-adrenergic receptor; TG: triglyceride; UCP1: uncoupling protein 1.