Impaired febrile response with age: role of thermogenesis in brown adipose tissue.
We demonstrated previously that in Escherichia coli-infected rats, the heat necessary for the febrile response is a result of thermogenesis in brown adipose tissue (BAT). To investigate whether senescent rats have an impaired febrile response to infection and whether such an impairment is a result of attenuated sympathetically activated thermogenesis in BAT, we assessed body temperature and the increase in mitochondrial guanosine 5'-diphosphate (GDP) binding sites in interscapular BAT in response to E. coli administration in young and senescent male F-344 rats. There was a significant delay of 2 hr in the onset of fever in the older animals. In addition, in senescent rats, the peak fever (1.0 +/- 0.1 delta degrees C vs 2.2 +/- 0.1) and the cumulative fever (383 +/- 43 delta degrees C.min vs 775 +/- 69) were significantly less than in the young rats (P less than 0.005). Baseline levels of GDP binding were the same in young and old rats. In young rats, during the rising phase of the fever, E. coli infection resulted in a 50% increase in the density of GDP binding sites in BAT mitochondria. In contrast, there was no increase in GDP binding in the older rats following infection. The failure to increase GDP binding may be a result of a reduced ability to unmask reserve GDP binding sites. Alternatively, there may be fewer total GDP binding sites (masked and unmasked) in senescent rats and these sites may already be unmasked. Collectively, these data suggest that the impaired febrile response with age is due to reduced thermogenesis in BAT.
Scarpace
P J
PJ
Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, Florida.
Matheny
M
M
Bender
B S
BS
Borst
S E
SE
D002001:Adipose Tissue, Brown / Q000378:metabolism* / Q000648:ultrastructure; D000375:Aging / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D001833:Body Temperature Regulation / Q000502:physiology*; D004927:Escherichia coli Infections / Q000503:physiopathology*; D005334:Fever / Q000503:physiopathology*; D006153:Guanosine Diphosphate / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D006153:Guanosine Diphosphate