Thermoregulation with age: role of thermogenesis and uncoupling protein expression in brown adipose tissue.

To investigate whether attenuation of thermogenesis in interscapular brown adipose tissue (IBAT) may account for the loss of thermoregulation with age, we examined two indices of thermogenesis after two types of cold exposure: one in which the senescent rats maintained homeothermy and the other in which the senescent rats became hypothermic. To this end, we assessed body temperature, guanosine 5'-diphosphate (GDP) binding to the IBAT mitochondrial uncoupling protein (UCP) and the induction of UCP mRNA after both 1-hr and 48-hr mild cold exposures at 8 degrees C and after a more severe, 1-hr cold exposure at 4 degrees C in 3- and 24-month-old F-344 rats. Thermoneutrality was determined to occur at an ambient temperature of 26 degrees C in rats of both ages. In the 1-hr mild cold-exposed rats, there was no significant increase in GDP binding to IBAT UCP. However, after 48 hr of mild cold exposure, there was a 3-fold increase in GDP binding and a 5-fold increase in the expression of UCP mRNA despite no hypothermia in either the young or old rats. During the more severe cold exposure, the senescent rats, but not the young rats, became hypothermic. GDP binding to UCP increased 75% following cold exposure and, surprisingly was the same in young and old rats. UCP transcripts did not increase during the 1-hr cold exposure. These data, coupled with our previous findings of diminished beta 3-agonist-stimulated IBAT thermogenesis, suggest that (i) IBAT thermogenesis, at least in the senescent rats, may be mediated by other than beta 3-adrenergic receptors, and (ii) that altered heat dissipation or impaired thermogenesis at some site other than interscapular BAT is responsible for the observed hypothermia.