Retinoid X receptor gamma-deficient mice have increased skeletal muscle lipoprotein lipase activity and less weight gain when fed a high-fat diet.
Fiche publication
Date publication
août 2004
Journal
Endocrinology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre, Dr KREZEL Wojciech
Tous les auteurs :
Haugen BR, Jensen DR, Sharma V, Pulawa LK, Hays WR, Krezel W, Chambon P, Eckel RH
Lien Pubmed
Résumé
Retinoids, derivatives of vitamin A, induce hypertriglyceridemia through decreased clearance of very low-density lipoprotein by a lipoprotein lipase (LPL)-dependent pathway. The retinoid X receptor (RXR) gamma isotype, which is highly expressed in skeletal muscle, may be important in mediating the effects of retinoids on skeletal muscle metabolism and triglyceride (TG) clearance. RXRgamma-deficient (-/-) mice had lower fasting plasma TG levels compared with wild-type littermates (33.1 +/- 2.0 vs. 51.7 +/- 6.3 mg/dl, respectively; P < 0.05). Skeletal muscle LPL activity was higher in RXRgamma mice (18.7 +/- 2.2 vs. 13.3 +/- 1.3 nmol free fatty acids/min.g; P = 0.03), but LPL activity was not different in adipose and cardiac tissue, suggesting a specific effect of RXRgamma in skeletal muscle. In addition, when exposed to a 14-wk high-fat diet, RXRgamma -/- mice had less weight gain, which was entirely due to lower fat mass (11.9 +/- 1.8 vs. 14.4 +/- 1.1 g; P = 0.01), and leptin levels were also lower in the RXRgamma -/- mice (17.6 +/- 5.0 vs. 30.9 +/- 6.4 ng/ml; P = 0.03). These data suggest that RXRgamma -/- mice are resistant to gain in fat mass in response to high-fat feeding. This occurs, at least in part, through up-regulation of LPL activity in skeletal muscle. An understanding of the mechanisms governing the role of RXR in TG disposal and metabolism may lead to the rational design of RXR-selective agonists and antagonists that may be useful in common disorders such as dyslipidemia and obesity.
Mots clés
Animals, Dietary Fats, administration & dosage, Lipoprotein Lipase, genetics, Mice, Muscle, Skeletal, enzymology, RNA, Messenger, analysis, Receptors, Retinoic Acid, deficiency, Retinoid X Receptors, Transcription Factors, deficiency, Weight Gain
Référence
Endocrinology. 2004 Aug;145(8):3679-85