title: 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.
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.
authors.affiliation: Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida, 33136, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Konstantin
authors.initials: K
authors.lastname: Levay
authors.forename: Tatyana
authors.initials: T
authors.lastname: Chanturiya
authors.forename: Galina
authors.initials: G
authors.lastname: Dvoriantchikova
authors.forename: Karen L
authors.initials: KL
authors.lastname: Anderson
authors.forename: Suzy D C
authors.initials: SD
authors.lastname: Bianco
authors.forename: Cintia B
authors.initials: CB
authors.lastname: Ueta
authors.forename: R Damaris
authors.initials: RD
authors.lastname: Molano
authors.forename: Antonello
authors.initials: A
authors.lastname: Pileggi
authors.forename: Eugenia V
authors.initials: EV
authors.lastname: Gurevich
authors.forename: Oksana
authors.initials: O
authors.lastname: Gavrilova
authors.forename: Vladlen Z
authors.initials: VZ
authors.lastname: Slepak
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000235:genetics*; D002395:Catecholamines / Q000652:urine; D059305:Diet, High-Fat; D004435:Eating; D004734:Energy Metabolism; D004837:Epinephrine / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics* / Q000502:physiology*; D006579:Heterozygote; D007328:Insulin / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity
chemical_list: D001786:Blood Glucose; D002395:Catecholamines; D044387:GTP-Binding Protein beta Subunits; C094668:Gnb5 protein, mouse; D007328:Insulin; D004837:Epinephrine