beta 3-Adrenergic receptor stimulation restores message and expression of brown-fat mitochondrial uncoupling protein in adult dogs

• Published in: Proceedings of the National Academy of Sciences - PNAS 1991-12, Vol.88 (23), p.10774-10777
• Main Authors: Champigny, O. (Centre de Recherche sur l'Endocrinologie Moleculaire et le Developement, Meudon-Bellevue, France), Ricquier, D, Blondel, O, Mayers, R.M, Briscoe, M.G, Holloway, B.R
• Format: Article
• Language: English
• Subjects: Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - physiology; Adrenergic beta-Agonists - pharmacology; Animals; Blotting, Northern; Body Weight - drug effects; Carrier Proteins - genetics; CHIEN; Dogs; ESTIMULO; Ion Channels; Membrane Proteins - genetics; Mitochondria - metabolism; Mitochondrial Proteins; MITOCHONDRIE; MITOCONDRIA; PERRO; Phenoxyacetates - pharmacology; Phenoxypropanolamines; PROTEINAS; PROTEINE; RECEPTEUR D'HORMONE; RECEPTORES DE HORMONAS; Receptors, Adrenergic, beta - drug effects; Receptors, Adrenergic, beta - physiology; RNA - drug effects; RNA - genetics; RNA - isolation & purification; RNA, Messenger - drug effects; RNA, Messenger - genetics; RNA, Messenger - isolation & purification; RNA, Mitochondrial; STIMULUS; TEJIDO ADIPOSO; TISSU ADIPEUX; Transcription, Genetic - drug effects; Uncoupling Protein 1
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.23.10774

Brown adipose tissue (BAT) is present throughout life in rodents and plays an important role in energy balance. However, whereas BAT is clearly recognizable in the neonates of larger mammals (including dogs, cats, sheep, cattle, and humans), it is undetectable or present in only small quantities in adults of these species and is replaced by a tissue with the gross characteristics of white adipose tissue. Here we provide evidence that treatment of adult dogs with a beta 3-adrenergic receptor agonist (ICI D7114) that has thermogenic and antiobesity properties leads to the appearance of BAT at several anatomical sites. The presence of BAT was primarily demonstrated by monitoring the inner mitochondrial membrane uncoupling protein and its mRNA, which are unique to the tissue. Neither message nor protein was detected in adipose tissue samples from control dogs but both were detected in samples from dogs treated with ICI D7114. The data suggest that stimulation of 63-adrenergic receptors can reactivate nascent BAT (which has the appearance of white adipose tissue) by increasing expression of the gene coding for uncoupling protein or lead to the recruitment of fully differentiated BAT from preadipocyte precursor cells