The effects of rexinoids and rosiglitazone on body weight and uncoupling protein isoform expression in the Zucker fa/fa rat

• Published in: Metabolism, clinical and experimental Vol. 49; no. 12; pp. 1610 - 1615
• Main Authors: Emilsson, Valur, O'Dowd, Jacqueline, Wang, Steven, Liu, Yong-Ling, Sennitt, Matthew, Heyman, Richard, Cawthorne, Michael A.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.2000; Elsevier
• Subjects: Adipose Tissue, Brown - metabolism; Animals; Biological and medical sciences; Body Weight - drug effects; Carrier Proteins - genetics; Carrier Proteins - metabolism; Eating - drug effects; Hormones. Endocrine system; Ion Channels; Medical sciences; Membrane Proteins - genetics; Membrane Proteins - metabolism; Membrane Transport Proteins; Mitochondrial Proteins; Nicotinic Acids - pharmacology; Obesity - metabolism; Obesity - pathology; Pharmacology. Drug treatments; Proteins - genetics; Proteins - metabolism; Rats; Rats, Zucker - anatomy & histology; Rats, Zucker - metabolism; Receptors, Retinoic Acid - agonists; Retinoid X Receptors; RNA, Messenger - metabolism; Rosiglitazone; Tetrahydronaphthalenes - pharmacology; Thiazoles - pharmacology; Thiazolidinediones; Transcription Factors - agonists; Uncoupling Protein 1; Uncoupling Protein 2; Uncoupling Protein 3; Weight Gain - drug effects; Endocrinopathy; Animal model; Obesity; Pancreatic hormone; Agonist; Uncoupling protein; Rat; Body weight; Rodentia; Nutrition disorder; Retinoid; Insulin; Target tissue resistance; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Rosiglitazone; Nutritional status; Comparative study; Biological receptor
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1053/meta.2000.18692

Agonists for the retinoid X receptor (RXR), the rexinoids, and the peroxisome proliferator-activated receptor gamma (PPAR γ), the thiazolidinediones, are effective in the treatment of insulin resistance in rodent models by enhancing insulin action and improving glycemic control. In the present study, we compared the effects of rexinoids and a thiazolidinedione on body weight and mitochondrial uncoupling protein (UCP) isoform mRNA expression in the obese Zucker fa/fa rat. Long-term (2 weeks) oral treatment with the rexinoids LG100268 and LG100324 reduced food intake and body weight gain, whereas rosiglitazone (BRL49653) tended to increase both food intake and weight gain. LG100268 and LG100324 increased brown adipose tissue (BAT) UCP-1 mRNA content by 2.7-fold ( P < .002) and 3.1-fold ( P < .001), respectively, while BRL49653 had no effect on BAT UCP-1 mRNA content. Neither the rexinoids nor the thiazolidinedione had any effect on the level of mRNA encoding UCP-2 and the recently described PPAR γ coactivator-1 (PGC-1). LG100324 increased UCP-3 mRNA content by 3.6-fold ( P < .0005) in muscle and 4.3-fold ( P < .0002) in white adipose tissue (WAT). LG100268 increased UCP-3 mRNA content in WAT by 2-fold ( P < .005) but was without any effect on muscle UCP-3. BRL49653 increased UCP-3 mRNA content by 2.1-fold ( P < .005) in muscle and 2.7-fold ( P < .003) in WAT. Thus, the rexinoids, but not the thiazolidinedione, have an antiobesity action by reducing food intake, and the increase in UCP-1 mRNA content in BAT may reflect a stimulation of BAT UCP-1 activity.