Potential involvement of mammalian and avian uncoupling proteins in the thermogenic effect of thyroid hormones

Thyroid hormones (THs) have long been known to be involved in the control of thermoregulation in birds and mammals. In particular, they are reported to play a role in the regulation of heat production. The underlying mechanisms could be the stimulation of the nuclear and mitochondrial transcription of several genes involved in energy metabolism and/or a direct action on the activity of components of the mitochondrial respiratory chain. Attention has recently been focussed on a subfamily of mitochondrial anion carriers called uncoupling proteins (UCPs). These proteins are suspected to be involved in a partial dissipation of the mitochondrial proton electrochemical gradient that would uncouple phosphorylations from oxidations and hence produce heat. However, the involvement of uncoupling mechanisms in thermogenesis and particularly in the thermogenic effect of TH is still unclear. The thermogenic role of UCP1, specifically expressed in brown adipose tissue, and its regulation by TH in rodents is quite well recognised, but the involvement in heat production of its mammalian homologues UCP2, ubiquitously expressed, and UCP3, muscle and adipose tissue-specific, as well as the role of the muscular avian UCP (avUCP), are to be further investigated. The expression of the UCP2 and UCP3 genes was shown to be enhanced by TH in muscle of several rodent species, and to be increased in situations where thermogenesis is stimulated, whereas results are more contrasted in pig. There is now increasing evidence that the physiological role of the mammalian UCP3 and UCP2 is rather related to lipid oxidation and/or prevention of reactive oxygen species accumulation than to heat production by uncoupling. The expression of avUCP was also recently demonstrated to be strongly regulated by thyroid status in chicken, and overexpressed in experimental conditions favouring high triiodothyronine concentrations and thermogenesis. However, its real uncoupling activity and contribution to thermogenesis remain to be established.