The steroid RU486 induces UCP1 expression in brown adipocytes.
RU486 (mifepristone), a potent antagonist at progesterone and glucocorticoid receptors (PR and GR), is well known for its use in the termination of unwanted pregnancies, the potential development of oral contraceptives, treatment of certain cancers and other activities. Potentially, it could also play a role in obesity control, although the few studies that have addressed this aspect have focused mainly on its central and anti-glucocorticoid effects. We have shown previously that it could have a direct effect on brown adipocytes in culture when administered together with progesterone. The aim of the present work was to analyse the effects of RU486 on the expression of uncoupling proteins (UCPs) in brown adipocytes. In culture-grown, differentiated brown adipocytes, placed in a serum-free medium to exclude the presence of progesterone or glucocorticoids, RU486 stimulated UCP1 expression at both the mRNA and protein levels. These effects could be mediated by PR, GR or other unknown mechanisms but do not seem to be due to its anti-progestin or anti-glucocorticoid actions. The results suggest that the steroid RU486 has a direct action on adipocytes which could be useful for stimulating non-shivering BAT thermogenesis and therefore is of interest in obesity studies.
Rodríguez
Ana M
AM
Departament de Biologia Fonamental i Ciències de la Salut, Ed. Guillem Colom, Universitat de les Illes Balears, Cra. Valldemossa, Km 7.5, 07122 Palma de Mallorca, Spain.
Palou
Andreu
A
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004734:Energy Metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology*; D007473:Ion Channels; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D015735:Mifepristone / Q000494:pharmacology*; D024101:Mitochondrial Proteins; D022722:Thermogenesis / Q000187:drug effects; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D016895:Culture Media, Serum-Free; D006727:Hormone Antagonists; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D015735:Mifepristone