Targeted deletion of one or two copies of the G protein beta subunit G beta 5 gene has distinct effects on body weight and behavior in mice

Article

关键词: RGS PROTEINS;    REGULATORS;    RECEPTOR;    FAMILY;    COMPLEX;    DOMAIN;    SELECTIVITY;    ACTIVATION;    MODULATOR;    SURVIVAL;   

DOI  :  10.1096/fj.11-190157

来源: SCIE

【 摘 要 】

We investigated the physiological role of G beta 5, a unique G protein beta subunit that dimerizes with regulators of G protein signaling (RGS) proteins of the R7 family instead of G gamma. G beta 5 is essential for stability of these complexes, so that its knockout (KO) causes degradation of the entire G beta 5-R7 family. We report that the G beta 5-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 G beta 5-R7 level can perturb normal animal metabolism and behavior. Our data on G beta 5 haploinsufficient mice may explain earlier observations of genetic linkage between R7 family mutations and obesity in humans.-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., and Slepak, V. Z. Targeted deletion of one or two copies of the G protein beta subunit G beta 5 gene has distinct effects on body weight and behavior in mice. FASEB J. 25, 3949-3957 (2011). www.fasebj.org

【 授权许可】

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