Up-regulation of a thermogenesis-related gene (UCP1) and down-regulation of PPAR gamma and aP2 genes in adipose tissue: possible features of the antiobesity effects of a beta 3-adrenergic agonist

A number of experiments have demonstrated the antiobesity effects of beta ( 3)-adrenergic receptor stimulation by promoting thermogenesis and/or lipoly sis. While many studies have been performed in order to develop beta (3)-ad renergic agonists as a novel strategy in the management of obesity, more in formation is needed about the mechanisms involved in thermogenesis and the actions of these drugs on adipocyte differentiation. To address this, the p ossible thermogenic and antiadipogenic properties of Tertatolol, a beta (3) -adrenergic agonist, in a diet-induced obesity model has been tested. Anima ls fed on a high-fat diet gained more weight and fat mass as compared with control and high-fat fed animals treated with Tertatolol. A RT-PCR was carr ied out in white adipose tissue specific genes involved in thermogenesis su ch as uncoupling proteins (UCPs) and adipogenesis such as peroxisome prolif erator-activated receptor (PPAR gamma2), retinoid receptors (RXR alpha /RAR alpha), and fatty acid binding protein (aP2). Levels of UCP1 mRNA were aug mented in the Tertatolol-treated group as compared to non-treated high-fat fed animals, while the beta (3)-adrenergic agonist treatment significantly decreased the expression levels of aP2 and transcription factors such as PP AR gamma2 and the ratio RXR alpha /RAR alpha as compared to obese rats. Alt ogether these data suggest that the antiobesity effects of beta (3)-adrener gic agonists are not limited to the promotion of thermogenesis and/or lipol ysis and support the implication that these beta (3)-adrenergic agonists al so affect fat deposition by impairing adipogenesis in white adipose tissue (WAT). (C) 2001 Elsevier Science Inc. All rights reserved.