Corticosterone decreases nonshivering thermogenesis and increases lipid storage in brown adipose tissue.
Brown adipose tissue (BAT) contains glucocorticoid receptors; glucocorticoids are required for maintaining differentiated BAT in culture. These studies were performed to determine the effects of corticosterone on BAT thermogenic function and lipid storage. Rats were adrenalectomized and given subcutaneous corticosterone pellets in concentrations that maintained plasma corticosterone constant across the range of 0-20 micrograms/dl or were sham adrenalectomized. All variables were examined 5 days after surgery and corticosterone replacement. Measures of BAT function-thermogenic capacity [guanosine 5'-diphosphate (GDP) binding and uncoupling protein (UCP; a BAT-specific thermogenic protein)] and storage (BAT wet wt, protein, and DNA levels) were made. Plasma hormones (corticosterone, adrenocorticotropic hormone, insulin, 3,3',5-triiodothyronine, and thyroxine were measured. Corticosterone significantly affected BAT thermogenic measures: UCP content and binding of GDP to BAT mitochondria decreased with increasing corticosterone; GDP binding characteristics in BAT from similarly prepared rats examined by Scatchard analysis showed that maximum binding (Bmax) and dissociation constant (Kd) decreased with increasing corticosterone dose. BAT DNA was increased by adrenalectomy and maintained at intact levels with all doses of corticosterone; BAT lipid storage increased dramatically at corticosterone values higher than the daily mean level in intact rats. Histologically, the number and size of lipid droplets within BAT adipocytes increased markedly with increased corticosterone. White adipose depots were more sensitive to circulating corticosterone concentrations than were BAT depots and increased in weight at levels of corticosterone that were at or below the daily mean level of intact rats. We conclude that, within its diurnal range of concentration corticosterone acts to inhibit nonshivering thermogenesis and increase lipid storage.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology, University of California, San Francisco 94143-0444.
A M
AM
Strack
M J
MJ
Bradbury
M F
MF
Dallman
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D004822:Epididymis; D006003:Glycogen / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D007473:Ion Channels; D050356:Lipid Metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013974:Thyroxine / Q000097:blood; D013997:Time Factors; D014284:Triiodothyronine / Q000097:blood; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D004343:Drug Implants; D007328:Insulin; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D000071256:Uncoupling Protein 1; D014284:Triiodothyronine; D006153:Guanosine Diphosphate; D000324:Adrenocorticotropic Hormone; D006003:Glycogen; D004247:DNA; D013974:Thyroxine; D003345:Corticosterone