Effects of the oral administration of a beta3-adrenergic agonist on lipid metabolism in alloxan-diabetic rats.
Previous studies have reported that beta3-adrenergic agonists regulate plasma glucose, triglycerides and free fatty acids in situations of hyperglycaemia and dyslipidaemia in rodents. In this study Trecadrine, a novel compound with affinity for beta3-adrenergic receptors, has been tested in an alloxan-induced model of hyperglycaemia in rats. Alloxan-induced hyperglycaemic rats were orally treated with Trecadrine (1 mg/kg/day for 4 days), resulting in an improvement of hyperglycaemia (from 16.6 to 8.3 mmol L(-1), P < 0.001). This effect was not associated with statistical differences in plasma insulin levels, which may be explained by changes in insulin resistance and carbohydrate oxidation in peripheral tissues. Furthermore, a reduction in internal white fat weight (-39%), which was not statistically significant, as well as in plasma triglycerides (from 1.89 to 0.33 mmol L(-1), P < 0.001) and free fatty acids (from 0.70 to 0.39 mmol L(-1), P < 0.001), was found after Trecadrine administration. Trecadrine apparently induced lipolytic activity in adipocytes, as suggested by the increase of oxygen consumption in white adipose tissue (+282%, P < 0.001), while free fatty acids decreased apparently through their utilisation in other tissues. Furthermore, the increase in brown adipose tissue oxygen consumption (+50%, P < 0.01) and in rectal temperature (P < 0.05) suggests that both glucose and fatty acid oxidation may be enhanced in this tissue. These results give support to the possible therapeutic use of beta3-adrenergic compounds in situations of hyperglycaemia, particularly when this is accompanied by hypertriglyceridaemia.
Department of Physiology and Nutrition, University of Navarra, Pamplona, Spain.
F I
FI
Milagro
J A
JA
Martínez
D000042:Absorption / Q000187:drug effects; D000284:Administration, Oral; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001592:Benzyl Alcohols / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D050260:Carbohydrate Metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D001592:Benzyl Alcohols; D020738:Leptin; C101319:trecadrine; D008071:Lipoprotein Lipase