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The genetic ablation of SRC-3 protects against obesity and improves insulin sensitivity by reducing the acetylation of PGC-1{alpha}.

Abstract : 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.
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https://www.hal.inserm.fr/inserm-00350742
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Submitted on : Wednesday, January 7, 2009 - 3:49:29 PM
Last modification on : Thursday, April 23, 2020 - 2:26:35 PM

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Agnès Coste, Jean-Francois Louet, Marie Lagouge, Carles Lerin, Maria Cristina Antal, et al.. The genetic ablation of SRC-3 protects against obesity and improves insulin sensitivity by reducing the acetylation of PGC-1{alpha}.. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2008, 105 (44), pp.17187-92. ⟨10.1073/pnas.0808207105⟩. ⟨inserm-00350742⟩

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