Human white adipocytes express the cold receptor TRPM8 which activation induces UCP1 expression, mitochondrial activation and heat production

•White adipocytes store lipids and brown adipocytes burn them generating ATP and heat.•Cold exposure activates brown adipocytes in vivo by stimulating the adrenergic system.•Cold is sensed by specific receptors, such as TRPM8, of peripheral nerve endings.•We demonstrate that the cold receptor TRPM8 is expressed in human white adipocytes.•Activation of TRPM8 induces a brown-like phenotype in human white adipocytes. Mammals possess two types of adipose tissue, white (WAT) and brown (BAT). The uncoupling protein 1 (UCP1) is a hallmark of BAT, being the pivotal player for cold-induced thermogenesis. WAT can acquire BAT characteristics with up-regulation of UCP1 after cold exposure or adrenergic stimulation. In the present study we demonstrated that human white adipocytes express the cold-sensing receptor TRPM8 which activation by menthol and icilin induced a rise in [Ca2+]i and UCP1 expression, increased mitochondrial membrane potential, glucose uptake and heat production. The induction of “brown-like” phenotype in human white adipocytes after TRPM8 activation was supported by ultrastructural morphological changes of mitochondrial morphology and of their intracellular localization, with no modifications of the genes regulating mitochondrial biogenesis. In conclusion human white adipocytes express the cold receptor TRPM8 which activation induces their “browning” supporting a possible role of this receptor in the control of adipose tissue metabolism and body energy balance.