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Title: The control of brown adipose tissue in the genetically obese Zucker (fa/fa) rat
Author: Holt, Susan Jayne
ISNI:       0000 0001 3580 9908
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 1984
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The binding of (3H)- GDP to brown adipose tissue (BAT) mitochondria was used as a measure of the thermogenic state of the tissue. A reduced level of GDP binding was observed in obese (fa/fa) rats, consistent with their impaired thermogenesis. The reduced GDP binding resulted from a reduction in the number of binding sites, and not from a change in affinity. BAT mitochondrial GDP binding was normalised in adrenalectomised fa/fa rats. Corticosterone replacement to adrenalectomised fa/fa rats restored the defect. The thermogenic response of BAT in fa/fa rats to changes in environmental temperature was normal in young (5 week old) rats but attenuated in older (10 week old) rats. At thermoneutrality, GDP binding in fa/fa rats was reduced when compared to lean rats. The BAT thermogenic response to sucrose overfeeding was absent in fa/fa rats, but was restored after adrenalectomy. Restriction of food intake reduced GDP binding in lean rats, but not in fa/fa rats. These results suggested that the reduced thermogenic capacity of fa/fa rats resulted from corticosteron inhibition of diet-related, but not cold-related BAT thermogenesis. Further experiments demonstrate that propranalol, a B antagonist, suppressed the level of BAT mitochondrial GDP binding of lean rats downto the levels of fa/fa rats and prevented the normalisation of GDP binding after adrenalectomy of fa/fa rats. These data have been interpreted as showing that the defect in diet-related BAT thermogenesis of fa/fa rats may reflect a corticosterone-dependent suppression of sympathetic stimulation to that tissue. The decrease in GDP binding in fa/fa rats was detected as early as 10 days of age, and was closely related to the fa gene concentration. The fa gene dependency was still apparent in the adult rat. Serum T3 levels were found to be related to the thermogenic state of BAT, in that they were reduced in fa/fa rats, raised after adrenalectomy, and suppressed again after corticosterone replacement. These levels were also raised on cold acclimation in lean and fa/fa rats, and by sucrose overfeeding in lean rats. However, T3 levels were not increased in sucrose-fed fa/fa rats. it is suggested that changes in serum T3 levels may be secondary to changes in sympathetic activity in BAT. Possible mechanisms for the control of diet-related sympathetic activity and BAT thermogenesis by glucocorticoids are discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Human anatomy & human histology