Enhanced acute response to corticosterone in genetically obese (ob/ob) mice.
Our previous work showed that ob/ob mice responded to physiological concentrations of blood corticosterone (maintained by implanted pellets of corticosterone in adrenalectomized mice) by increasing food intake and blood insulin concentration to a much greater extent than did lean mice. The present study sought to determine whether the chronic presence of corticosterone was necessary or whether a single injection would also have these effects. Lean and ob/ob mice were adrenalectomized at 4.5 wk of age, injected with corticosterone at 10.5 wk of age, and killed 6 or 15 h after injection. A markedly exaggerated hyperinsulinemia was seen in ob/ob mice at 15 h. Food intake increased in both lean and obese mice, and brown adipose tissue thermogenesis (as reflected by mitochondrial guanosine 5'-diphosphate binding) was suppressed in both. We conclude that the ob/ob mouse has an excessive central sensitivity and responsiveness to a rapid action of corticosterone that results in neural activation of insulin secretion and suppression of brown adipose tissue thermogenesis. The persistence of some degree of obesity in the adrenalectomized ob/ob mouse is attributed to the remaining slight hyperinsulinemia coupled with reduced energy expenditure due to persistent thermoregulation at a lower than normal body temperature.
Tokuyama
K
K
Department of Biochemistry, University of Ottawa, Ontario, Canada.
Himms-Hagen
J
J
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000502:physiology; D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology*; D004343:Drug Implants; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D006153:Guanosine Diphosphate / Q000378:metabolism; D007328:Insulin / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL / Q000502:physiology; D008820:Mice, Obese / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D012016:Reference Values
D001786:Blood Glucose; D004343:Drug Implants; D007328:Insulin; D006153:Guanosine Diphosphate; D003345:Corticosterone