Acute injection of beta-adrenoceptor agonist BRL 35135 corrects both impaired uncoupling protein and lipoprotein lipase gene expression but not hypercapacity of lipogenesis in brown adipose tissue of suckling fa/fa rats.
This study was undertaken to determine whether acute injection of the beta-adrenoceptor BRL 35135, which is known to activate thermogenesis, could correct the earliest detectable metabolic abnormalities that characterize brown (BAT) and white (WAT) adipose tissues of pre-obese Zucker rats. In 14-day-old pups, a single intraperitoneal injection of BRL (10 micrograms/g, 3 h before sacrifice) had no effect on uncoupling protein mRNA content in BAT of lean pups, whereas the low level of this mRNA was restored to normal in pre-obese rats. Both lipoprotein lipase (LPL) activity and mRNA content, which were decreased in BAT of pre-obese compared to lean pups (-60%), were stimulated after BRL injection. However, this effect was more pronounced in fa/fa than in Fa/fa rats (+100% and +50%, respectively). In BAT, the increase in fatty acid synthetase (FAS) activity observed in fa/fa rats compared to their lean Fa/fa littermates was not reduced. In WAT, the stimulation of beta-adrenergic receptors had no effect on lipid storage capacity, since FAS and LPL activities remained unchanged. In conclusion, pre-obese Zucker fa/fa rats are responsive to BRL 35135 treatment: acute administration of this drug was able to improve impaired thermogenesis and to correct temporarily other abnormalities of early emergence in BAT. This treatment had no effect in WAT. Taken together, our data reinforce the hypothesis that reduced sympathetic activity in BAT is one of the primary lesions of the obese rat which may play a key role in the development of this genetic obesity.
Marie
V
V
Institut National de la Santé et de la Recherche Médicale, U 177, Paris, France.
Dupuy
F
F
Bazin
R
R
D000273:Adipose Tissue / Q000201:enzymology / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D000833:Animals, Suckling; D001483:Base Sequence; D001786:Blood Glucose / Q000187:drug effects; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D064429:Fatty Acid Synthases / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005838:Genotype; D007328:Insulin / Q000097:blood; D007473:Ion Channels; D008055:Lipids / Q000096:biosynthesis; D008071:Lipoprotein Lipase / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D010627:Phenethylamines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012337:RNA, Ribosomal, 18S / Q000737:chemistry; D051381:Rats; D011924:Rats, Zucker; D014475:Uncoupling Agents / Q000378:metabolism; D000071256:Uncoupling Protein 1
D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D002352:Carrier Proteins; D007328:Insulin; D007473:Ion Channels; D008055:Lipids; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010627:Phenethylamines; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1; C063157:BRL 35135; D064429:Fatty Acid Synthases; D008071:Lipoprotein Lipase