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

84 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Melanocortins
GTP-Binding Proteins
Central Nervous System
Mothers
Obesity
Mutation
Alleles
Cyclic AMP Receptors
Germ-Line Mutation
Paraventricular Hypothalamic Nucleus
Knockout Mice
Energy Metabolism
Hypothalamus
Insulin Resistance
Eating
Brain

Keywords

  • HUMDISEASE
  • MOLNEURO

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Central Nervous System Imprinting of the G Protein Gsα and Its Role in Metabolic Regulation. / Chen, Min; Wang, Jie; Dickerson, Kathryn E.; Kelleher, James; Xie, Tao; Gupta, Divakar; Lai, Edwin W.; Pacak, Karel; Gavrilova, Oksana; Weinstein, Lee S.

In: Cell Metabolism, Vol. 9, No. 6, 14.05.2009, p. 548-555.

Research output: Contribution to journalArticle

Chen, M, Wang, J, Dickerson, KE, Kelleher, J, Xie, T, Gupta, D, Lai, EW, Pacak, K, Gavrilova, O & Weinstein, LS 2009, 'Central Nervous System Imprinting of the G Protein Gsα and Its Role in Metabolic Regulation', Cell Metabolism, vol. 9, no. 6, pp. 548-555. https://doi.org/10.1016/j.cmet.2009.05.004
Chen, Min ; Wang, Jie ; Dickerson, Kathryn E. ; Kelleher, James ; Xie, Tao ; Gupta, Divakar ; Lai, Edwin W. ; Pacak, Karel ; Gavrilova, Oksana ; Weinstein, Lee S. / Central Nervous System Imprinting of the G Protein Gsα and Its Role in Metabolic Regulation. In: Cell Metabolism. 2009 ; Vol. 9, No. 6. pp. 548-555.
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