Effect of the beta-adrenoceptor agonist BRL 26830 on fatty acid synthesis and on the activities of pyruvate dehydrogenase and acetyl-CoA carboxylase in adipose tissues of the rat.
BRL 26830 is a thermogenic beta-adrenoceptor agonist which stimulates lipolysis and fatty acid oxidation in vivo. It also stimulates insulin secretion, and hence promotes glucose utilisation in vivo. The effect of this agent on white and brown adipose tissue of the rat was investigated. BRL 26830 increased the rate of fatty acid synthesis in vivo in white adipose tissue by 135% but reduced the rate of fatty acid synthesis in vivo in brown adipose tissue by 78%. The increase was abolished in white adipose tissue of streptozotocin-diabetic rats, indicating that the effect involved a rise in circulating insulin levels. The reduction in fatty acid synthesis in brown adipose tissues was associated with a reduction in the activity of acetyl-CoA carboxylase in the tissue consistent with a direct beta-adrenoceptor-mediated effect. BRL 26830 also increased the proportion of pyruvate dehydrogenase in its active form in vivo in brown adipose tissue and this increase was abolished in streptozotocin-diabetic rats. These findings illustrate different sensitivities of white and brown adipose tissues to combined beta-adrenergic and insulin stimulation.
Wilson
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S
Beecham Pharmaceuticals Research Division, Biosciences Research Centre, Epsom, Surrey.
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000502:physiology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004983:Ethanolamines / Q000494:pharmacology*; D005227:Fatty Acids / Q000096:biosynthesis*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D005227:Fatty Acids; D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; C039248:BRL 26830A; D000103:Acetyl-CoA Carboxylase