Central Nervous System Imprinting of the G Protein Gsα and Its Role in Metabolic Regulation

Min Chen, Jie Wang, Kathryn E. Dickerson, James Kelleher, Tao Xie, Divakar Gupta, Edwin W. Lai, Karel Pacak, Oksana Gavrilova, Lee S. Weinstein

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

In Albright hereditary osteodystrophy, a monogenic obesity disorder linked to heterozygous mutations of Gsα, 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 Gsα mutation develop obesity, insulin resistance, and diabetes. These parent-of-origin effects are due to Gsα imprinting, with preferential expression from the maternal allele in some tissues. As Gsα is ubiquitously expressed, the tissue involved in this metabolic imprinting effect is unknown. Using brain-specific Gsα knockout mice, we show that Gsα imprinting within the central nervous system underlies these effects and that Gsα is imprinted in the paraventricular nucleus of the hypothalamus. Maternal Gsα 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 Gsα-dependent and -independent pathways.

Original languageEnglish (US)
Pages (from-to)548-555
Number of pages8
JournalCell Metabolism
Volume9
Issue number6
DOIs
StatePublished - May 14 2009

Keywords

  • HUMDISEASE
  • MOLNEURO

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Central Nervous System Imprinting of the G Protein G<sub>s</sub>α and Its Role in Metabolic Regulation'. Together they form a unique fingerprint.

  • Cite this

    Chen, M., Wang, J., Dickerson, K. E., Kelleher, J., Xie, T., Gupta, D., Lai, E. W., Pacak, K., Gavrilova, O., & Weinstein, L. S. (2009). Central Nervous System Imprinting of the G Protein Gsα and Its Role in Metabolic Regulation. Cell Metabolism, 9(6), 548-555. https://doi.org/10.1016/j.cmet.2009.05.004