title: Effects of deficiency of the G protein Gsα on energy and glucose homeostasis.
abstract: G(s)α is a ubiquitously expressed G protein α-subunit that couples receptors to the generation of intracellular cyclic AMP. The G(s)α gene GNAS is a complex gene that undergoes genomic imprinting, an epigenetic phenomenon that leads to differential expression from the two parental alleles. G(s)α is imprinted in a tissue-specific manner, being expressed primarily from the maternal allele in a small number of tissues. Albright hereditary osteodystrophy is a monogenic obesity disorder caused by heterozygous G(s)α mutations but only when the mutations are maternally inherited. Studies in mice indicate a similar parent-of-origin effect on energy and glucose metabolism, with maternal but not paternal mutations leading to obesity, reduced sympathetic nerve activity and energy expenditure, glucose intolerance and insulin resistance, with no primary effect on food intake. These effects result from G(s)α imprinting leading to severe G(s)α deficiency in one or more regions of the central nervous system, and are associated with a specific defect in melanocortins to stimulate sympathetic nerve activity and energy expenditure.
authors.affiliation: Signal Transduction Section, National Institute of Diabetes and Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. minc@intra.niddk.nih.gov
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Nemechek
authors.forename: Eralda
authors.initials: E
authors.lastname: Mema
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Lee S
authors.initials: LS
authors.lastname: Weinstein
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D009154:Mutation
chemical_list: D019205:GTP-Binding Protein alpha Subunits, Gs; D005947:Glucose