HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 28, 18989-18999, July 14, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/28/18989    most recent M511752200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Xie, T. Articles by Weinstein, L. S. Search for Related Content PubMed PubMed Citation Articles by Xie, T. Articles by Weinstein, L. S. Social Bookmarking                      What's this?

The Alternative Stimulatory G Protein -Subunit XLs Is a Critical Regulator of Energy and Glucose Metabolism and Sympathetic Nerve Activity in Adult Mice^*

Tao Xie, Antonius Plagge, Oksana Gavrilova^¶, Stephanie Pack^¶, William Jou^¶, Edwin W. Lai^||**, Marga Frontera, Gavin Kelsey, and Lee S. Weinstein¹

From the Metabolic Diseases Branch and ^¶Mouse Metabolism Core Laboratory, NIDDK, ^||Reproductive Biology and Medicine Branch, NICHD, and ^**Clinical Neurocardiology Section, NINDS, National Institutes of Health, Bethesda, Maryland 20892 and Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge CB2 4AT, United Kingdom

The complex imprinted Gnas locus encodes several gene products including G_s, the ubiquitously expressed G protein -subunit required for receptor-stimulated cAMP generation, and the neuroendocrine-specific G_s isoform XLs. XLs is only expressed from the paternal allele, whereas G_s is biallelically expressed in most tissues. XLs knock-out mice (Gnasxl^m+/p–) have poor suckling and perinatal lethality, implicating XLs as critical for postnatal feeding. We have now examined the metabolic phenotype of adult Gnasxl^m+/p– mice. Gnasxl^m+/p– mice had reduced fat mass and lipid accumulation in adipose tissue, with increased food intake and metabolic rates. Gene expression profiling was consistent with increased lipid metabolism in adipose tissue. These changes likely result from increased sympathetic nervous system activity rather than adipose cell-autonomous effects, as we found that XLs is not normally expressed in adult adipose tissue, and Gnasxl^m+/p– mice had increased urinary norepinephrine levels but not increased metabolic responsiveness to a 3-adrenergic agonist. Gnasxl^m+/p– mice were hypolipidemic and had increased glucose tolerance and insulin sensitivity. The similar metabolic profile observed in some prior paternal Gnas knock-out models results from XLs deficiency (or deficiency of the related alternative truncated protein XLN1). XLs (or XLN1) is a negative regulator of sympathetic nervous system activity in mice.

Received for publication, October 31, 2005 , and in revised form, April 19, 2006.

^* This work was supported by the NIDDK, National Institutes of Health Intramural Research Program, United States Department of Health and Human Services. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains a supplemental table.

¹ To whom correspondence should be addressed: Metabolic Diseases Branch, NIDDK/National Institutes of Health, Bldg. 10 Rm. 8C101, Bethesda, MD 20892-1752. Tel.: 301-402-2923; Fax: 301-402-0374; E-mail: leew{at}amb.niddk.nih.gov.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. Xie, M. Chen, O. Gavrilova, E. W. Lai, J. Liu, and L. S. Weinstein Severe Obesity and Insulin Resistance due to Deletion of the Maternal Gs{alpha} Allele Is Reversed by Paternal Deletion of the Gs{alpha} Imprint Control Region Endocrinology, May 1, 2008; 149(5): 2443 - 2450. [Abstract] [Full Text] [PDF]

				A. Plagge, G. Kelsey, and E. L Germain-Lee Physiological functions of the imprinted Gnas locus and its protein variants G{alpha}s and XL{alpha}s in human and mouse J. Endocrinol., February 1, 2008; 196(2): 193 - 214. [Abstract] [Full Text] [PDF]

				T. Xie, M. Chen, Q.-H. Zhang, Z. Ma, and L. S. Weinstein cell-specific deficiency of the stimulatory G protein {alpha}-subunit Gs{alpha} leads to reduced cell mass and insulin-deficient diabetes PNAS, December 4, 2007; 104(49): 19601 - 19606. [Abstract] [Full Text] [PDF]

				D. N. Long, S. McGuire, M. A. Levine, L. S. Weinstein, and E. L. Germain-Lee Body Mass Index Differences in Pseudohypoparathyroidism Type 1a Versus Pseudopseudohypoparathyroidism May Implicate Paternal Imprinting of G{alpha}s in the Development of Human Obesity J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 1073 - 1079. [Abstract] [Full Text] [PDF]