Central nervous system imprinting of the G protein G(s)alpha and its role in metabolic regulation.

Published

Journal Article

In Albright hereditary osteodystrophy, a monogenic obesity disorder linked to heterozygous mutations of G(s)alpha, the G protein that mediates receptor-stimulated cAMP generation, obesity develops only when the mutation is on the maternal allele. Likewise, mice with maternal (but not paternal) germline G(s)alpha mutation develop obesity, insulin resistance, and diabetes. These parent-of-origin effects are due to G(s)alpha imprinting, with preferential expression from the maternal allele in some tissues. As G(s)alpha is ubiquitously expressed, the tissue involved in this metabolic imprinting effect is unknown. Using brain-specific G(s)alpha knockout mice, we show that G(s)alpha imprinting within the central nervous system underlies these effects and that G(s)alpha is imprinted in the paraventricular nucleus of the hypothalamus. Maternal G(s)alpha mutation impaired melanocortin stimulation of energy expenditure but did not affect melanocortin's effect on food intake, suggesting that melanocortins may regulate energy balance in the central nervous system through both G(s)alpha-dependent and -independent pathways.

Full Text

Duke Authors

Cited Authors

  • Chen, M; Wang, J; Dickerson, KE; Kelleher, J; Xie, T; Gupta, D; Lai, EW; Pacak, K; Gavrilova, O; Weinstein, LS

Published Date

  • June 2009

Published In

Volume / Issue

  • 9 / 6

Start / End Page

  • 548 - 555

PubMed ID

  • 19490909

Pubmed Central ID

  • 19490909

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2009.05.004

Language

  • eng

Conference Location

  • United States