%0 Journal Article %T The genetic ablation of SRC-3 protects against obesity and improves insulin sensitivity by reducing the acetylation of PGC-1{alpha}. %+ Institut de génétique et biologie moléculaire et cellulaire (IGBMC) %+ Department of Molecular and Cellular Biology %+ Department of Cell Biology Harvard Medical School %+ Institut Clinique de la Souris (ICS) %A Coste, Agnès %A Louet, Jean-Francois %A Lagouge, Marie %A Lerin, Carles %A Antal, Maria Cristina %A Meziane, Hamid %A Schoonjans, Kristina %A Puigserver, Pere %A O'Malley, Bert, W. %A Auwerx, Johan %< avec comité de lecture %@ 0027-8424 %J Proceedings of the National Academy of Sciences of the United States of America %I National Academy of Sciences %V 105 %N 44 %P 17187-92 %8 2008-11-04 %D 2008 %R 10.1073/pnas.0808207105 %M 18957541 %Z Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]Journal articles %X Transcriptional control of metabolic circuits requires coordination between specific transcription factors and coregulators and is often deregulated in metabolic diseases. We characterized here the mechanisms through which the coactivator SRC-3 controls energy homeostasis. SRC-3 knock-out mice present a more favorable metabolic profile relative to their wild-type littermates. This metabolic improvement in SRC-3(-/-) mice is caused by an increase in mitochondrial function and in energy expenditure as a consequence of activation of PGC-1alpha. By controlling the expression of the only characterized PGC-1alpha acetyltransferase GCN5, SRC-3 induces PGC-1alpha acetylation and consequently inhibits its activity. Interestingly, SRC-3 expression is induced by caloric excess, resulting in the inhibition of PGC-1alpha activity and energy expenditure, whereas caloric restriction reduces SRC-3 levels leading to enhanced PGC-1alpha activity and energy expenditure. Collectively, these data suggest that SRC-3 is a critical link in a cofactor network that uses PGC-1alpha as an effector to control mitochondrial function and energy homeostasis. %G English %L inserm-00350742 %U https://inserm.hal.science/inserm-00350742 %~ INSERM %~ CNRS %~ UNIV-STRASBG1 %~ IGBMC %~ UNIV-STRASBG %~ SITE-ALSACE