Effect of the beta-adrenoceptor agonist BRL-35135 on development of obesity in suckling Zucker (fa/fa) rats.
This study was undertaken to determine whether administration of a thermogenic beta-agonist drug to Zucker fatty rats could correct some of the earliest metabolic defects detectable in brown adipose tissue (BAT). Fa/fa and fa/fa littermates were given oral administration of BRL-35135 from 8 to 16 days of age. In fa/fa rats, the lipid content of white and brown adipose tissues was significantly reduced. In the BAT of fa/fa rats, thermogenic capacity was restored to the level observed in Fa/fa rats, whereas hyperactivity of fatty acid synthetase was abolished, and a deficit in lipoprotein lipase (activity and mRNA) was partly corrected. Hyperinsulinemia in fa/fa pups was significantly reduced. The decreased content of GLUT-4 mRNA that characterized BAT of fa/fa pups was also restored to normal. At variance with observations in preobese rats, BRL had very little or no effect on lean Fa/fa rats. The present study reveals that chronic administration of a beta-agonist drug early in life prevents emergence of most of the metabolic abnormalities that characterize fa/fa rats at the onset of obesity. This suggests that impaired sympathetic activity may play a role in the development of this genetic obesity.
Charon
C
C
Institut National de la Santé et de la Recherche Médicale, U177, Paris, France.
Dupuy
F
F
Marie
V
V
Bazin
R
R
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D001833:Body Temperature Regulation; D002352:Carrier Proteins / Q000096:biosynthesis; D064429:Fatty Acid Synthases / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D051275:Glucose Transporter Type 4; D006153:Guanosine Diphosphate / Q000378:metabolism; D007473:Ion Channels; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000096:biosynthesis; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis; D009124:Muscle Proteins; D009765:Obesity / Q000235:genetics / Q000503:physiopathology* / Q000517:prevention & control; D009838:Oligodeoxyribonucleotides; D010627:Phenethylamines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012337:RNA, Ribosomal, 18S / Q000096:biosynthesis; D051381:Rats; D011924:Rats, Zucker; D013851:Thinness; D000071256:Uncoupling Protein 1
D000318:Adrenergic beta-Agonists; D002352:Carrier Proteins; D005230:Fatty Acids, Nonesterified; D051275:Glucose Transporter Type 4; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009838:Oligodeoxyribonucleotides; D010627:Phenethylamines; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; C495694:Slc2a4 protein, rat; D000071256:Uncoupling Protein 1; D006153:Guanosine Diphosphate; C063157:BRL 35135; D064429:Fatty Acid Synthases; D008071:Lipoprotein Lipase