Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cabrero, A.
Right arrow Articles by Vázquez, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cabrero, A.
Right arrow Articles by Vázquez, M.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Diabetes 50:1883-1890, 2001
© 2001 by the American Diabetes Association, Inc.

Bezafibrate Reduces mRNA Levels of Adipocyte Markers and Increases Fatty Acid Oxidation in Primary Culture of Adipocytes

Àgatha Cabrero, Marta Alegret, Rosa M. Sánchez, Tomás Adzet, Juan C. Laguna, and Manuel Vázquez

Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain

The molecular mechanisms by which peroxisome proliferator–activated receptor (PPAR) activation by fibrates reduces fat deposition and improves insulin sensitivity are not completely understood. We report that exposure of a rat primary culture of adipocytes for 24 h to the PPAR activator bezafibrate increased the mRNA levels of crucial genes involved in peroxisomal and mitochondrial ß-oxidation. The mRNA levels of the peroxisomal ß-oxidation rate-limiting enzyme acyl-CoA oxidase and of the muscle-type carnitine palmitoyl transferase I (M-CPT-I), which determines the flux of mitochondrial ß-oxidation, increased by 1.6-fold (P < 0.02) and 4.5-fold (P = 0.001), respectively. These changes were accompanied by an increase in the transcript levels of the uncoupling protein-2 (UCP-2; 1.5-fold induction; P < 0.05) and UCP-3 (3.7-fold induction; P < 0.001), mitochondrial proteins that reduce ATP yield and may facilitate the oxidation of fatty acids. Furthermore, bezafibrate increased the mRNA levels of the fatty acid translocase (2-fold induction; P < 0.01), suggesting a higher fatty acid uptake into adipocytes. In agreement with these changes, bezafibrate caused a 1.9-fold induction (P < 0.02) in 9,10-[3H]palmitate oxidation. Moreover, bezafibrate reduced the mRNA expression of several adipocyte markers, including PPAR{gamma} (30% reduction; P = 0.05), tumor necrosis factor-{alpha} (33% reduction; P < 0.05), and the ob gene (26% reduction). In contrast, adipocyte fatty acid binding protein mRNA levels increased (1.5-fold induction; P < 0.01), pointing to a mobilization of fatty acids to mitochondria and peroxisomes. The reduction of the adipocyte markers caused by bezafibrate was accompanied by an increase in the mRNA levels of the preadipocyte marker Pref-1 (1.6-fold induction; P < 0.01). Some of the changes observed in the primary culture of rat adipocytes also were studied in the epididymal white adipose tissue of bezafibrate-treated rats for 7 days. In vivo, M-CPT-I mRNA levels increased (4.5-fold induction; P = 0.001) in epididymal white adipose tissue of bezafibrate-treated rats. Similarly, fatty acid translocase (2.6-fold induction; P = 0.002) and Pref-1 (5.6-fold induction) mRNA levels increased, although differences in the latter were not significant because of huge individual variations. These results indicate that exposure of adipocytes to bezafibrate, independent of its hepatic effects, increases the degradation of fatty acids, reducing their availability to synthesize triglycerides. As a result, some degree of dedifferentiation of adipocytes to preadipocyte-like cells is achieved. These changes may be involved in the reduction in fat depots and in the improvement of insulin sensitivity observed after bezafibrate treatment.


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 EndocrinologyHome page
J. Mercader, J. Ribot, I. Murano, F. Felipe, S. Cinti, M. L. Bonet, and A. Palou
Remodeling of White Adipose Tissue after Retinoic Acid Administration in Mice
Endocrinology, November 1, 2006; 147(11): 5325 - 5332.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M. J. Yoon, G. Y. Lee, J.-J. Chung, Y. H. Ahn, S. H. Hong, and J. B. Kim
Adiponectin Increases Fatty Acid Oxidation in Skeletal Muscle Cells by Sequential Activation of AMP-Activated Protein Kinase, p38 Mitogen-Activated Protein Kinase, and Peroxisome Proliferator-Activated Receptor {alpha}
Diabetes, September 1, 2006; 55(9): 2562 - 2570.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
A. Planavila, R. Rodriguez-Calvo, A. F. de Arriba, R. M. Sanchez, J. C. Laguna, M. Merlos, and M. Vazquez-Carrera
Inhibition of Cardiac Hypertrophy by Triflusal (4-Trifluoromethyl Derivative of Salicylate) and Its Active Metabolite
Mol. Pharmacol., April 1, 2006; 69(4): 1174 - 1181.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
Y. Li, P. Wang, J. Xu, and G. V. Desir
Voltage-gated potassium channel Kv1.3 regulates GLUT4 trafficking to the plasma membrane via a Ca2+-dependent mechanism
Am J Physiol Cell Physiol, February 1, 2006; 290(2): C345 - C351.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. Jove, A. Planavila, R. M. Sanchez, M. Merlos, J. C. Laguna, and M. Vazquez-Carrera
Palmitate Induces Tumor Necrosis Factor-{alpha} Expression in C2C12 Skeletal Muscle Cells by a Mechanism Involving Protein Kinase C and Nuclear Factor-{kappa}B Activation
Endocrinology, January 1, 2006; 147(1): 552 - 561.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Planavila, J. C. Laguna, and M. Vazquez-Carrera
Nuclear Factor-{kappa}B Activation Leads to Down-regulation of Fatty Acid Oxidation during Cardiac Hypertrophy
J. Biol. Chem., April 29, 2005; 280(17): 17464 - 17471.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
R Serrano, M Villar, C Martinez, J M Carrascosa, N Gallardo, and A Andres
Differential gene expression of insulin receptor isoforms A and B and insulin receptor substrates 1, 2 and 3 in rat tissues: modulation by aging and differentiation in rat adipose tissue
J. Mol. Endocrinol., February 1, 2005; 34(1): 153 - 161.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Xu, P. Wang, Y. Li, G. Li, L. K. Kaczmarek, Y. Wu, P. A. Koni, R. A. Flavell, and G. V. Desir
The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity
PNAS, March 2, 2004; 101(9): 3112 - 3117.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M. Laplante, H. Sell, K. L. MacNaul, D. Richard, J. P. Berger, and Y. Deshaies
PPAR-{gamma} Activation Mediates Adipose Depot-Specific Effects on Gene Expression and Lipoprotein Lipase Activity: Mechanisms for Modulation of Postprandial Lipemia and Differential Adipose Accretion
Diabetes, February 1, 2003; 52(2): 291 - 299.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
J. KOPECKY, P. FLACHS, K. BARDOVA, P. BRAUNER, T. PRAZAK, and J. SPONAROVA
Modulation of Lipid Metabolism by Energy Status of Adipocytes: Implications for Insulin Sensitivity
Ann. N.Y. Acad. Sci., June 1, 2002; 967(1): 88 - 101.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2001 by the American Diabetes Association.