Thermoregulation with age: restoration of beta(3)-adrenergic responsiveness in brown adipose tissue by cold exposure.
The beta(3)-adrenergic-stimulated thermogenic response in brown adipose tissue (BAT) is impaired in senescent rats, whereas cold-induced thermogenesis is not. To determine if cold exposure can restore beta(3)-adrenergic receptor responsiveness in senescent rats, we examined BAT mitochondrial GDP binding in young and old rats, and UCP mRNA levels in young rats following stimulation by the beta(3)-adrenergic agonist CGP-12177 with and without prior cold exposure. F-344 male rats were maintained at thermoneutrality or exposed to 8 degrees C for 48 hr, followed by a 24-hr period of rewarming before administration of 0.75 mg/kg CGP-12177 or vehicle solution. During the rewarming period, GDP binding remained elevated but UCP mRNA levels with a half-life of 11 hr returned to levels observed in the thermoneutral controls. In young rats, both cold exposure and administration of the beta(3)-adrenergic agonist to thermoneutral controls increased GDP binding 2-fold and UCP mRNA levels 4-fold. However, in cold-exposed young rats, there was no further increase with beta(3)-agonist treatment. In senescent control rats, CGP-12177 did not increase GDP binding, but cold exposure did. However, in cold-exposed old rats, the beta(3)-agonist was now able to increase GDP binding. The induction of UCP mRNA by CGP-12177 was also investigated and found to be 25% less in senescent compared with young rats. These observations indicate that cold exposure restores the impaired beta(3)-adrenergic signal transduction in BAT from senescent rats. One possibility is that cold exposure induces the synthesis of one or more components in the beta(3)-adrenergic pathway in senescent rats.
Scarpace
P J
PJ
Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Medical Center, Gainsville, Florida 32608-1197, USA.
Tse
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Matheny
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D002001:Adipose Tissue, Brown / Q000502:physiology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology*; D003080:Cold Temperature; D006153:Guanosine Diphosphate / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D008565:Membrane Proteins; D011412:Propanolamines; D012333:RNA, Messenger; D006153:Guanosine Diphosphate; C033394:CGP 12177