Targeted deletion of one or two copies of the G protein β subunit Gβ5 gene has distinct effects on body weight and behavior in mice

Qiang Wang, Konstantin Levay, Tatyana Chanturiya, Galina Dvoriantchikova, Karen L. Anderson, Suzy D.C. Bianco, Cintia B. Ueta, R. Damaris Molano, Antonello Pileggi, Eugenia V. Gurevich, Oksana Gavrilova, Vladlen Z. Slepak

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

We investigated the physiological role of Gβ5, a unique G protein β subunit that dimerizes with regulators of G protein signaling (RGS) proteins of the R7 family instead of Gγ. Gβ5 is essential for stability of these complexes, so that its knockout (KO)causes degradation of the entire Gβ5-R7 family. We report that the Gβ5-KO mice remain leaner than the wild type (WT) throughout their lifetime and are resistant to a high-fat diet. They have a 5-fold increase in locomotor activity, increased thermogenesis, and lower serum insulin, all of which correlate with a higher level of secreted epinephrine. Heterozygous (HET) mice are 2-fold more active than WT mice. Surprisingly, with respect to body weight, the HET mice display a phenotype opposite to that of the KO mice: by the age of 6 mo, they are ≥15% heavier than the WT and have increased adiposity, insulin resistance, and liver steatosis. These changes occur in HET mice fed a normal diet and without apparent hyperphagia, mimicking basic characteristics of human metabolic syndrome. We conclude that even a partial reduction in Gβ5-R7 level can perturb normal animal metabolism and behavior. Our data on Gβ5 haploinsufficient mice may explain earlier observations of genetic linkage between R7 family mutations and obesity in humans.

Original languageEnglish (US)
Pages (from-to)3949-3957
Number of pages9
JournalFASEB Journal
Volume25
Issue number11
DOIs
StatePublished - Nov 2011

Keywords

  • Insulin
  • Obesity
  • Pancreas
  • RGS protein
  • RGS7

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

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    Wang, Q., Levay, K., Chanturiya, T., Dvoriantchikova, G., Anderson, K. L., Bianco, S. D. C., Ueta, C. B., Molano, R. D., Pileggi, A., Gurevich, E. V., Gavrilova, O., & Slepak, V. Z. (2011). Targeted deletion of one or two copies of the G protein β subunit Gβ5 gene has distinct effects on body weight and behavior in mice. FASEB Journal, 25(11), 3949-3957. https://doi.org/10.1096/fj.11-190157