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Horm Metab Res 2014; 46(12): 841-844
DOI: 10.1055/s-0034-1387798
Review
© Georg Thieme Verlag KG Stuttgart · New York

Role of Gsα in Central Regulation of Energy and Glucose Metabolism

L. S. Weinstein
1   Signal Transduction Section, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, USA
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Further Information

Publication History

received 12 May 2014

accepted 06 August 2014

Publication Date:
18 September 2014 (online)

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Abstract

GNAS is a complex imprinted locus with multiple oppositely imprinted gene products, including the G protein α-subunit Gsα that is expressed primarily from the maternal allele in some tissues and the Gsα isoform XLαs that is expressed only from the paternal allele. Maternal Gsα mutations in mice and in patients with Albright hereditary osteodystrophy lead to obesity, insulin resistance, and hyperlipidemia. Studies in mice show that these effects are primarily due to Gsα imprinting in the central nervous system and that Gsα deficiency in one or more regions of the central nervous system lead to reduced sympathetic nervous system and energy expenditure without affecting food intake. Loss of Gsα in the central nervous system appears to lead to these effects primarily through impairment of melanocortin signaling. Loss of XLαs in mice leads to opposite effects on energy and glucose metabolism.

Key words

genomic imprinting - obesity - pseudohypoparathyroidism - Albright hereditary osteodystrophy
 

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