|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 275, Issue 44, 34797-34802, November 3, 2000
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Catecholamines play an important role in
controlling white adipose tissue function and development.
Expression of Human
2-Adrenergic Receptors in Adipose Tissue
of 
3-Adrenergic Receptor-deficient Mice Promotes Diet-induced
Obesity*
§¶,¶,,,
,,,¶¶
Beth Israel Deaconess Medical Center and
Harvard Medical School, Boston, Massachusetts 02215, the
§ INSERM U317, Institut Louis Bugnard,
Université Paul Sabatier, CHR Rangueil, 31403 Toulouse Cedex 4, France, the Institute of Normal Human Morphology, University of
Ancona, 60020 Ancona, Italy, the ** Department of Microbiology and
Cancer Center, University of Pennsylvania, Philadelphia,
Pennsylvania 19104, and the §§ Section of
Gastroenterology, Department of Medicine, University of Chicago,
Chicago, Illinois 60637
- and
2-adrenergic receptors (ARs) couple positively and negatively,
respectively, to adenylyl cyclase and are co-expressed in human
adipocytes. Previous studies have demonstrated increased adipocyte
2/-AR balance in obesity, and it has been proposed that increased
2-ARs in adipose tissue with or without decreased -ARs may
contribute mechanistically to the development of increased fat mass. To
critically test this hypothesis, adipocyte 2/-AR balance was
genetically manipulated in mice. Human 2A-ARs were transgenically
expressed in the adipose tissue of mice that were either homozygous
(
/) or heterozygous (+/) for a disrupted
3-AR allele. Mice expressing 2-ARs in fat, in
the absence of 3-ARs (3-AR / background), developed high fat
diet-induced obesity. Strikingly, this effect was due entirely to
adipocyte hyperplasia and required the presence of 2-ARs, the
absence of 3-ARs, and a high fat diet. Of note, obese 2-transgenic, 3 / mice failed to develop insulin resistance, which may reflect the fact that expanded fat mass was due to adipocyte hyperplasia and not adipocyte hypertrophy. In summary, we have demonstrated that increased 2/-AR balance in adipocytes promotes obesity by stimulating adipocyte hyperplasia. This study also demonstrates one way in which two genes (2 and
3-AR) and diet interact to influence fat mass.
*
This work was supported by the National Institutes of
Health, the Boston/Obesity Nutrition Research Center Transgenic
Core, and Eli Lilly.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present Address: Dept. of Biochemistry, Molecular Biology, and
Cell Biology, Northwestern University, Evanston, IL 60201.
¶¶
To whom correspondence should be addressed: Beth Israel
Deaconess Medical Center and Harvard Medical School, RN-325,
Div. of Endocrinology, 330 Brookline Ave., Boston, MA 02215. Tel.: 617-667-5954; Fax: 617-667-2927; E-mail:
blowell@caregroup.harvard.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  T. J. Bartness and C. K. Song Thematic review series: Adipocyte Biology. Sympathetic and sensory innervation of white adipose tissue J. Lipid Res., August 1, 2007; 48(8): 1655 - 1672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Jaworski, E. Sarkadi-Nagy, R. E. Duncan, M. Ahmadian, and H. S. Sul Regulation of Triglyceride Metabolism. * IV. Hormonal regulation of lipolysis in adipose tissue Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G1 - G4. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Daviaud, J. Boucher, S. Gesta, C. Dray, C. Guigne, D. Quilliot, A. Ayav, O. Ziegler, C. Carpene, J.-S. Saulnier-Blache, et al. TNF{alpha} up-regulates apelin expression in human and mouse adipose tissue FASEB J, July 1, 2006; 20(9): 1528 - 1530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Boucher, B. Masri, D. Daviaud, S. Gesta, C. Guigne, A. Mazzucotelli, I. Castan-Laurell, I. Tack, B. Knibiehler, C. Carpene, et al. Apelin, a Newly Identified Adipokine Up-Regulated by Insulin and Obesity Endocrinology, April 1, 2005; 146(4): 1764 - 1771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Genetically Modified Animals in Endocrinology Endocr. Rev., June 1, 2004; 25(3): 512 - 519. [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Young, J. Weiss, and N. Boufath Effects of Dietary Monosaccharides on Sympathetic Nervous System Activity in Adipose Tissues of Male Rats Diabetes, May 1, 2004; 53(5): 1271 - 1278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Pedersen, K. Kristensen, P. A. Hermann, J. A. Katzenellenbogen, and B. Richelsen Estrogen Controls Lipolysis by Up-Regulating {alpha}2A-Adrenergic Receptors Directly in Human Adipose Tissue through the Estrogen Receptor {alpha}. Implications for the Female Fat Distribution J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1869 - 1878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lucas, G. Tavernier, C. Tiraby, A. Mairal, and D. Langin Expression of human hormone-sensitive lipase in white adipose tissue of transgenic mice increases lipase activity but does not enhance in vitro lipolysis J. Lipid Res., January 1, 2003; 44(1): 154 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Rodriguez-Cuenca, E. Pujol, R. Justo, M. Frontera, J. Oliver, M. Gianotti, and P. Roca Sex-dependent Thermogenesis, Differences in Mitochondrial Morphology and Function, and Adrenergic Response in Brown Adipose Tissue J. Biol. Chem., November 1, 2002; 277(45): 42958 - 42963. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Philipp, M. Brede, and L. Hein Physiological significance of alpha 2-adrenergic receptor subtype diversity: one receptor is not enough Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2002; 283(2): R287 - R295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Valet, G. Tavernier, I. Castan-Laurell, J. S. Saulnier-Blache, and D. Langin Understanding adipose tissue development from transgenic animal models J. Lipid Res., June 1, 2002; 43(6): 835 - 860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Weinstein, S. Yu, D. R. Warner, and J. Liu Endocrine Manifestations of Stimulatory G Protein {alpha}-Subunit Mutations and the Role of Genomic Imprinting Endocr. Rev., October 1, 2001; 22(5): 675 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Visentin, N. Morin, E. Fontana, D. Prevot, J. Boucher, I. Castan, P. Valet, D. Grujic, and C. Carpene Dual Action of Octopamine on Glucose Transport into Adipocytes: Inhibition via beta 3-Adrenoceptor Activation and Stimulation via Oxidation by Amine Oxidases J. Pharmacol. Exp. Ther., October 1, 2001; 299(1): 96 - 104. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |