Uncoupling proteins 2 and 3 with age: regulation by fasting and beta3-adrenergic agonist treatment

In rodents, adaptive thermogenesis in brown adipose tissue (BAT) serves both to regulate body mass after hyperphagia and to conserve energy during food deprivation. In addition to uncoupling protein 1 (UCP1), UCP3 and possibly UCP2 may have a role in energy homeostasis in BAT. We examined basal levels of UCP2 and UCP3 mRNA with age and regulation of UCP1, UCP2, and UCP3 mRNA by two conditions known to modulate energy homeostasis: fasting and beta3-adrenergic agonists. UCP1, UCP2, and UCP3 mRNA levels were unchanged between 3, 24, and 31 months of age in BAT, and UCP2 and UCP3 mRNA levels were unchanged between 6 and 24 months of age in retroperitoneal white adipose tissue (RTWAT). Following a 2-day fast, there were sizable reductions in BAT UCP1 and UCP3 mRNA, but these decreases with fasting were significantly less in the older compared with the young rats. Fasting had no effect on UCP2 mRNA levels at any age. The beta3-adrenergic agonist, CL316,243, increased BAT UCP1 and UCP3 mRNA equally in both young and old rats. The beta3-adrenergic agonist did not increase UCP2 mRNA in BAT but did increase expression in RTWAT of both young and old rats. In summary, these data indicate that the expression of the three uncoupling proteins is unchanged with age. Although the upregulation of these uncoupling proteins by beta3-adrenergic agonist treatment is maintained with age, the downregulation by fasting is diminished with age. The parallel regulation of UCP1 and UCP3 expression in BAT suggests that UCP3, like UCP1, may have a role in energy homeostasis in BAT. The diminished downregulation of UCP1 and UCP3 expression in BAT by fasting suggests that energy conservation in response to food deprivation is impaired with age, and this may contribute to an inability of older animals to maintain body mass during periods when food is limited.