Up-regulation of a thermogenesis-related gene (UCP1) and down-regulation of PPARgamma and aP2 genes in adipose tissue: possible features of the antiobesity effects of a beta3-adrenergic agonist.
A number of experiments have demonstrated the antiobesity effects of beta(3)-adrenergic receptor stimulation by promoting thermogenesis and/or lipolysis. While many studies have been performed in order to develop beta(3)-adrenergic agonists as a novel strategy in the management of obesity, more information is needed about the mechanisms involved in thermogenesis and the actions of these drugs on adipocyte differentiation. To address this, the possible thermogenic and antiadipogenic properties of Tertatolol, a beta(3)-adrenergic agonist, in a diet-induced obesity model has been tested. Animals 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 carried out in white adipose tissue specific genes involved in thermogenesis such as uncoupling proteins (UCPs) and adipogenesis such as peroxisome proliferator-activated receptor (PPARgamma2), retinoid receptors (RXRalpha/RARalpha), and fatty acid binding protein (aP2). Levels of UCP1 mRNA were augmented 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 PPARgamma2 and the ratio RXRalpha/RARalpha as compared to obese rats. Altogether these data suggest that the antiobesity effects of beta(3)-adrenergic agonists are not limited to the promotion of thermogenesis and/or lipolysis and support the implication that these beta(3)-adrenergic agonists also affect fat deposition by impairing adipogenesis in white adipose tissue (WAT).
Margareto
J
J
Department of Physiology and Nutrition, University of Navarra, Pamplona, Spain.
Larrarte
E
E
Marti
A
A
Martinez
J A
JA
D033962:Adaptor Protein Complex 2; D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D007473:Ion Channels; D020738:Leptin / Q000097:blood; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000378:metabolism*; D000071256:Uncoupling Protein 1; D015854:Up-Regulation
D033962:Adaptor Protein Complex 2; D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D019440:Anti-Obesity Agents; D002352:Carrier Proteins; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000607073:Rara protein, rat; D022702:Receptors, Adrenergic, beta-3; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D014157:Transcription Factors; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1