Chronic administration of BRL 26830A for 9 weeks improves insulin sensitivity but does not prevent weight gain in gold-thioglucose obese mice.
BRL 26830A, a beta adrenoceptor agonist, has been shown to have antiobesity and antidiabetic properties in rodents. The aim of this study was to study the effects of chronic BRL 26830A treatment (20 mg/kg/day for 9 weeks) on weight gain and the development of insulin resistance in gold-thioglucose-injected mice (GTG). BRL 26830A slowed the rate of weight gain in GTG such that mice weighed significantly less between 2 w and 7 w of treatment. However, at the time of sacrifice (9 w), there was no difference in body weight between treated and untreated GTG. The obesity-induced reduction in lipogenesis in brown adipose tissue (BAT) was increased 9 fold to greater than CON levels. However, weight and fatty acid (FA) content of BAT were reduced, suggesting increased lipid turnover and thermogenesis. Lipogenesis, FA content and fat pad weight were unchanged in white adipose tissue (WAT) and decreased in liver of GTG. Glucose tolerance was improved in both CON and GTG. Hyperglycemia, hyperinsulinemia and changes in cardiac and hepatic glucose oxidation as indicated by PDHC activity were normalized. Serum triglycerides and non-esterified fatty acids were reduced. Thus, chronic BRL 26830A treatment prevented the development of insulin resistance and attenuated weight gain, but did not prevent the development of obesity in this model.
Bryson
J M
JM
Department of Endocrinology, Royal Prince Alfred Hospital, University of Sydney, NSW, Australia. j.bryson@biochem.usyd.edu.au
Wensley
V R
VR
Phuyal
J L
JL
Caterson
I D
ID
Cooney
G J
GJ
D000273:Adipose Tissue / Q000737:chemistry; D002001:Adipose Tissue, Brown / Q000737:chemistry / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000818:Animals; D006051:Aurothioglucose; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D004983:Ethanolamines / Q000627:therapeutic use*; D005227:Fatty Acids / Q000032:analysis; D006003:Glycogen / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008055:Lipids / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009765:Obesity / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D004983:Ethanolamines; D005227:Fatty Acids; D007328:Insulin; D008055:Lipids; D011768:Pyruvate Dehydrogenase Complex; D006051:Aurothioglucose; C039248:BRL 26830A; D006003:Glycogen