Uncoupling proteins (UCPs) are inner mitochondrial membrane transporters that dissipate the
proton gradient, releasing stored energy as heat, without coupling to other energy-consuming processes. Therefore, the UCPs are thought to be important determinants of the metabolic efficiency. To elucidate relationships between the UCPs expressions and
insulin sensitivity improvement, we treated KK-Ay mice with
beta 3 adrenergic receptor agonist for 21 days and examined the changes of the UCPs
mRNA expressions in various tissues. Chronic treatment of a specific
beta 3 adrenergic receptor agonist,
CL316,243 (0.2 mg/kg
body weight/day s.c.) markedly increased the expressions of
uncoupling protein 1 (UCP1),
uncoupling protein 2 (UCP2), and
uncoupling protein 3 (UCP3) by 14-fold, 6-fold, and 16-fold, respectively, in the brown adipose tissue (BAT). The UCP1 and UCP3
mRNA expressions in the white adipose tissue (WAT) were also increased by 12-fold and 9-fold, respectively, but the UCP2
mRNA expression was not changed in this tissue. Interestingly, the UCP2 and UCP3
mRNA expressions were strikingly decreased in the skeletal muscle and heart. Particularly, the UCP3
mRNA expression level in the skeletal muscle was dropped to 10% of that of the saline-treated control mice, indicating that the UCPs
mRNA expressions are regulated in tissue-specific ways. The concentrations of plasma
insulin and circulating
free fatty acid (FFA) were significantly decreased, suggesting that they correlate with the reductions of the UCP2 and UCP3
mRNA expressions in the skeletal muscle and heart. It has been thought that the UCP1 and UCP3
mRNA expressions in the BAT and WAT are mainly controlled by the hypothalamus via the sympathetic nervous system, while the levels of
insulin, FFA or both may play important roles in the control of the UCP2 and UCP3
mRNA expressions in the skeletal muscle an heart.