title: GRK2 contribution to the regulation of energy expenditure and brown fat function.
abstract: Obesity is a major health problem and an important risk factor for the development of multiple disorders. Previous studies in our laboratory have revealed that down-regulation of GRK2 decreases age-related adiposity, but the physiological and molecular mechanisms underlying this outcome remain unclear. We evaluate whether the lean phenotype results from a direct effect of GRK2 on energy homeostasis. The study of white adipose tissue (WAT) in wild-type (WT) and GRK2(+/-) littermates showed a reduced expression of lipogenic enzymes and enhanced lipolytic rate in adult GRK2(+/-) mice. Moreover, hemizygous mice display higher energy expenditure and lower respiratory exchange ratio. Analysis of brown adipose tissue (BAT) from adult GRK2(+/-) mice showed a less deteriorated morphology associated with age compared to WT, which is correlated with a higher basal core temperature. BAT from young GRK2(+/-) mice showed an increase in gene expression of thermogenesis-related genes. Accordingly, hemizygous mice displayed better thermogenic capacity and exhibited a more oxidative phenotype in both BAT and WAT than WT littermates. Overexpression of GRK2 in brown adipocytes corroborated the negative effect of this kinase in BAT function and differentiation. Collectively, our data point to GRK2 inhibition as a potential tool for the enhancement of brown fat activity, which may have important therapeutic implications for the treatment of obesity and associated metabolic disorders.
authors.affiliation: Department of Biochemistry and Molecular Biology II, School of Pharmacy, Complutense University-Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Madrid, Spain.
authors.forename: Rocio
authors.initials: R
authors.lastname: Vila-Bedmar
authors.forename: Lucia
authors.initials: L
authors.lastname: Garcia-Guerra
authors.forename: Iria
authors.initials: I
authors.lastname: Nieto-Vazquez
authors.forename: Federico
authors.initials: F
authors.lastname: Mayor
authors.forename: Margarita
authors.initials: M
authors.lastname: Lorenzo
authors.forename: Cristina
authors.initials: C
authors.lastname: Murga
authors.forename: Sonia
authors.initials: S
authors.lastname: Fernández-Veledo
mesh_terms: D002001:Adipose Tissue, Brown / Q000502:physiology*; D052436:Adipose Tissue, White / Q000378:metabolism; D000375:Aging / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation; D004734:Energy Metabolism / Q000502:physiology*; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D057898:Hemizygote; D051379:Mice; D009765:Obesity / Q000235:genetics*; D022722:Thermogenesis / Q000502:physiology
chemical_list: C496568:GRK2 protein, mouse; D054769:G-Protein-Coupled Receptor Kinase 2