Uncoupling proteins 2 and 3 with age: Regulation by fasting and beta(3)-adrenergic agonist treatment

In rodents, adaptive thermogenesis in brown adipose tissue (BAT) serves bot h to regulate body mass after hyperphagia and to conserve energy during foo d deprivation. In addition to uncoupling protein 1 (UCP1), UCP3 and possibl y UCP2 may have a role in energy homeostasis in BAT. We examined basal leve ls of UCP2 and UCP3 mRNA with age and regulation of UCP1, UCP2, and UCP3 mR NA by two conditions known to modulate energy homeostasis: fasting and beta (3),-adrenergic agonists. UCP1, UCP1, and UCP3 mRNA levels were unchanged between 3, 24, and 31 months of age in BAT, and UCP2 and UCP3 mRNA levels w ere unchanged between 6 and 24 months of age in retroperitoneal white adipo se tissue (RTWAT). Following a 2-day; fast, there were sizable reductions i n BAT UCP1 and UCP3 mRNA, but these decreases with fasting were significant ly less in the older compared with the young rats. Fasting had no effect on UCP2 mRNA levels at any age. The beta (3)-adrenergic agonist, CL316,243, i ncreased RAT UCP1 and UCP3 mRNA equally in both young and old rats. The bet a (3)-adrenergic agonist did not increase UCP2 mRNA in BET but did increase expression in RTWAT of both young and old rats. In summary, these data ind icate that the expression of the three uncoupling proteins is unchanged wit h age. Although the upregulation of these uncoupling proteins by beta (3)-a drenergic agonist treatment is maintained with age, the downregulation by f asting is diminished with age. The parallel regulation of UCP1 and UCP3 exp ression in BAT suggests that UCP3, like UCP1, may have a role in energy hom eostasis in BAT. The diminished downregutation of UCP1 and UCP3 expression in BAT by fasting suggests that energy conservation in response to food dep rivation is impaired with age, and this may contribute to an inability of o lder animals to maintain body mass during periods when food is limited.