Genetically obese C57BL/6 ob/ob mice respond normally to sympathomimetic compounds.
The suggestion that defective thermoregulatory thermogenesis in the genetically obese (ob/ob) mouse is due to a low thermic response to noradrenaline has been investigated using both noradrenaline and the longer-acting sympathomimetic compounds, ephedrine and BRL 26830A. Below thermoneutrality (23.5 degrees C) the metabolic rate of obese mice was lower than that of their lean littermates, whereas at a thermoneutral temperature (31 degrees C) the metabolic rate of the obese mice was as high as that of lean mice. This confirms the view that the ob/ob mouse has defective thermoregulatory thermogenesis. However, in C57BL/6 mice, this defect is not due to a failure to respond to noradrenaline, because at 31 degrees C the maximum thermic effects of noradrenaline, ephedrine and BRL 26830A were as high in obese as in lean mice and at 23.5 degrees C they were higher in obese than in lean mice. Furthermore, the response of brown adipose tissue to beta-adrenoceptor stimulation appears normal since noradrenaline caused a normal rise in brown adipose tissue temperature, and treatment with noradrenaline or BRL 26830A in vivo caused a normal increase in GDP binding by brown adipose tissue mitochondria. At 31 degrees C propranolol depressed metabolic rate equally in lean and obese C57BL/6 mice, whereas at 23.5 degrees C it depressed metabolic rate more in lean than obese mice. In contrast to C57BL/6 mice, Aston ob/ob mice showed a reduced thermic response to noradrenaline. These results suggest that defective thermoregulatory thermogenesis in the ob/ob mouse is primarily due to a reduced ability to raise sympathetic tone, but in some strains an additional failure in the thermic response to noradrenaline may develop.
D002001:Adipose Tissue, Brown / Q000503:physiopathology; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects; D004809:Ephedrine / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D006153:Guanosine Diphosphate / Q000378:metabolism; D007700:Kinetics; D008660:Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000503:physiopathology*; D011433:Propranolol / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology*
D004983:Ethanolamines; D013566:Sympathomimetics; D006153:Guanosine Diphosphate; C039248:BRL 26830A; D011433:Propranolol; D004809:Ephedrine; D009638:Norepinephrine