QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.105.015040v1 69/2/471    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gary-Bobo, M. Articles by Bensaid, M. Search for Related Content PubMed PubMed Citation Articles by Gary-Bobo, M. Articles by Bensaid, M.

The Cannabinoid CB1 Receptor Antagonist Rimonabant (SR141716) Inhibits Cell Proliferation and Increases Markers of Adipocyte Maturation in Cultured Mouse 3T3 F442A Preadipocytes

CNS Research Department, Sanofi-Aventis Research, Montpellier, France

Adipocyte cell proliferation is an important process in body fat mass development in obesity. Adiponectin or Acrp30 is an adipocytokine exclusively expressed and secreted by adipose tissue that regulates lipid and glucose metabolism and plays a key role in body weight regulation and homeostasis. Adiponectin mRNA expression in adipose tissue and plasma level of adiponectin are decreased in obesity and type 2 diabetes. In obese rodents, the selective CB₁ receptor antagonist rimonabant reduces food intake and body weight and improves lipid and glucose parameters. We have reported previously that rimonabant stimulated adiponectin mRNA expression in adipose tissue of obese fa/fa rats, by a direct effect on adipocytes. We report here that rimonabant (10–400 nM) inhibits cell proliferation of cultured mouse 3T3 F442A preadipocytes in a concentration-dependent manner. In parallel to this inhibitory effect on preadipocyte cell proliferation, rimonabant (25–100 nM) stimulates mRNA expression and protein levels of two late markers of adipocyte differentiation (adiponectin and glyceraldehyde-3-phosphate dehydrogenase) with a maximal effect at 100 nM, without inducing the accumulation of lipid droplets. Furthermore, treatment of mouse 3T3 F442A preadipocytes with rimonabant (100 nM) inhibits basal and serum-induced p42/44 mitogen-activated protein (MAP) kinase activity. These results suggest that inhibition of MAP kinase activity by rimonabant may be one of mechanisms involved in the inhibition of 3T3 F442A preadipocyte cell proliferation and stimulation of adiponectin and GAPDH expression. The inhibition of preadipocyte cell proliferation and the induction of adipocyte late "maturation" may participate in rimonabant-induced antiobesity effects, particularly the reduction of body fat mass.

Address correspondence to: Mohammed Bensaid, Sanofi-Aventis, CNS Research Department, 371 rue du Professeur J. Blayac, F-34184 Montpellier Cédex 04, France. E-mail: mohammed.bensaid{at}sanofi-aventis.com

This article has been cited by other articles:

				R. W. Nesto and K. Mackie Endocannabinoid system and its implications for obesity and cardiometabolic risk Eur. Heart J. Suppl., March 1, 2008; 10(suppl_B): B34 - B41. [Abstract] [Full Text] [PDF]

				C. Pagano, C. Pilon, A. Calcagno, R. Urbanet, M. Rossato, G. Milan, K. Bianchi, R. Rizzuto, P. Bernante, G. Federspil, et al. The Endogenous Cannabinoid System Stimulates Glucose Uptake in Human Fat Cells via Phosphatidylinositol 3-Kinase and Calcium-Dependent Mechanisms J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4810 - 4819. [Abstract] [Full Text] [PDF]

				M. Bifulco, C. Grimaldi, P. Gazzerro, S. Pisanti, and A. Santoro Rimonabant: Just an Antiobesity Drug? Current Evidence on Its Pleiotropic Effects Mol. Pharmacol., June 1, 2007; 71(6): 1445 - 1456. [Abstract] [Full Text] [PDF]

				M. Bluher, S. Engeli, N. Kloting, J. Berndt, M. Fasshauer, S. Batkai, P. Pacher, M. R. Schon, J. Jordan, and M. Stumvoll Dysregulation of the Peripheral and Adipose Tissue Endocannabinoid System in Human Abdominal Obesity Diabetes, November 1, 2006; 55(11): 3053 - 3060. [Abstract] [Full Text] [PDF]

				D. Sarnataro, S. Pisanti, A. Santoro, P. Gazzerro, A. M. Malfitano, C. Laezza, and M. Bifulco The Cannabinoid CB1 Receptor Antagonist Rimonabant (SR141716) Inhibits Human Breast Cancer Cell Proliferation through a Lipid Raft-Mediated Mechanism Mol. Pharmacol., October 1, 2006; 70(4): 1298 - 1306. [Abstract] [Full Text] [PDF]

				P. F. Pilch and N. Bergenhem Pharmacological Targeting of Adipocytes/Fat Metabolism for Treatment of Obesity and Diabetes Mol. Pharmacol., September 1, 2006; 70(3): 779 - 785. [Abstract] [Full Text] [PDF]

				I. Matias, M.-P. Gonthier, P. Orlando, V. Martiadis, L. De Petrocellis, C. Cervino, S. Petrosino, L. Hoareau, F. Festy, R. Pasquali, et al. Regulation, Function, and Dysregulation of Endocannabinoids in Models of Adipose and {beta}-Pancreatic Cells and in Obesity and Hyperglycemia J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 3171 - 3180. [Abstract] [Full Text] [PDF]