anisomycin and Obesity

An obese (ob) gene product, expressed specifically in adipose tissues, regulates energy balance. Here we report adipocytes in adipose tissue actually express ob mRNA and that a synthetic glucocorticoid (dexamethasone) regulates expression of the ob gene. Addition of 100 nM dexamethasone to isolated rat adipocytes rapidly induced a 4-8 fold increase in ob mRNA. This increase in ob mRNA level was apparent within 1 h, and reached a maximum at about 7 h after stimulation. The dexamethasone-stimulated increase of ob mRNA was only partially blocked by protein synthesis inhibitors cycloheximide (20 micrograms/ml) or anisomycin (200 microM). This suggests that new protein synthesis is not necessarily required for the observed dexamethasone-stimulated increase in ob mRNA.

Topics: 1-Methyl-3-isobutylxanthine; 3T3 Cells; Adipocytes; Adipose Tissue; Adipose Tissue, Brown; Animals; Anisomycin; Cell Differentiation; Cells, Cultured; Cycloheximide; Dexamethasone; Epididymis; Gene Expression; Male; Mice; Muscle, Smooth, Vascular; Obesity; Protein Synthesis Inhibitors; Rats; Rats, Sprague-Dawley; RNA, Messenger

A single intracerebroventricular injection of dexamethasone rapidly (within 30 min) decreases brown adipose tissue thermogenesis by 25% as assessed by GDP binding and increases plasma insulin twofold in adrenalectomized ob/ob mice. The present study investigated the type of corticoid receptor(s) that mediate these effects and determined whether protein synthesis was necessary for expression of these glucocorticoid actions in ob/ob mice. Intracerebroventricular injection of aldosterone (a type I-corticoid receptor agonist) was ineffective in altering peripheral metabolism in adrenalectomized ob/ob mice, whereas RU-486 (a type II-corticoid receptor antagonist) abolished the effects of dexamethasone. Thus type II-like corticoid receptors, not type I receptors, mediated the rapid effects of dexamethasone in adrenalectomized ob/ob mice. Anisomycin (0.5 mg) administered subcutaneously almost completely suppressed (-92%) cerebral protein synthesis, but anisomycin did not abolish the rapid effects of dexamethasone in adrenalectomized ob/ob mice. Thus protein synthesis is not a prerequisite for rapid effects of dexamethasone in adrenalectomized ob/ob mice.

Topics: Adipose Tissue, Brown; Adrenalectomy; Animals; Anisomycin; Brain; Dexamethasone; Guanosine Diphosphate; Insulin; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mifepristone; Obesity; Oxygen Consumption; Protein Biosynthesis; Receptors, Glucocorticoid