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


ABSTRACT: We investigated the physiological role of G?5, a unique G protein ? subunit that dimerizes with regulators of G protein signaling (RGS) proteins of the R7 family instead of G?. G?5 is essential for stability of these complexes, so that its knockout (KO)causes degradation of the entire G?5-R7 family. We report that the G?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?5-R7 level can perturb normal animal metabolism and behavior. Our data on G?5 haploinsufficient mice may explain earlier observations of genetic linkage between R7 family mutations and obesity in humans.

SUBMITTER: Wang Q 

PROVIDER: S-EPMC3205839 | biostudies-other | 2011 Nov

REPOSITORIES: biostudies-other

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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.

Wang Qiang Q   Levay Konstantin K   Chanturiya Tatyana T   Dvoriantchikova Galina G   Anderson Karen L KL   Bianco Suzy D C SD   Ueta Cintia B CB   Molano R Damaris RD   Pileggi Antonello A   Gurevich Eugenia V EV   Gavrilova Oksana O   Slepak Vladlen Z VZ  

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20110730 11


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 therm  ...[more]

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