Metabolic reprogramming by Acly inhibition using SB-204990 alters glucoregulation and modulates molecular mechanisms associated with aging
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Published:2023-03-08
Issue:1
Volume:6
Page:
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ISSN:2399-3642
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Container-title:Communications Biology
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language:en
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Short-container-title:Commun Biol
Author:
Sola-García Alejandro, Cáliz-Molina María Ángeles, Espadas IsabelORCID, Petr MichaelORCID, Panadero-Morón Concepción, González-Morán DanielORCID, Martín-Vázquez María Eugenia, Narbona-Pérez Álvaro JesúsORCID, López-Noriega Livia, Martínez-Corrales GuillermoORCID, López-Fernández-Sobrino RaúlORCID, Carmona-Marin Lina M., Martínez-Force EnriqueORCID, Yanes OscarORCID, Vinaixa MariaORCID, López-López DanielORCID, Reyes José CarlosORCID, Dopazo JoaquínORCID, Martín Franz, Gauthier Benoit R.ORCID, Scheibye-Knudsen MortenORCID, Capilla-González VivianORCID, Martín-Montalvo AlejandroORCID
Abstract
AbstractATP-citrate lyase is a central integrator of cellular metabolism in the interface of protein, carbohydrate, and lipid metabolism. The physiological consequences as well as the molecular mechanisms orchestrating the response to long-term pharmacologically induced Acly inhibition are unknown. We report here that the Acly inhibitor SB-204990 improves metabolic health and physical strength in wild-type mice when fed with a high-fat diet, while in mice fed with healthy diet results in metabolic imbalance and moderated insulin resistance. By applying a multiomic approach using untargeted metabolomics, transcriptomics, and proteomics, we determined that, in vivo, SB-204990 plays a role in the regulation of molecular mechanisms associated with aging, such as energy metabolism, mitochondrial function, mTOR signaling, and folate cycle, while global alterations on histone acetylation are absent. Our findings indicate a mechanism for regulating molecular pathways of aging that prevents the development of metabolic abnormalities associated with unhealthy dieting. This strategy might be explored for devising therapeutic approaches to prevent metabolic diseases.
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Reference81 articles.
1. Shields, M. & Martel, L. Healthy living among seniors. Health Rep. 16, 7–20 (2006). 2. Walston, J. D. Sarcopenia in older adults. Curr. Opin. Rheumatol. 24, 623–627 (2012). 3. Kuznetsova, T., Prange, K. H. M., Glass, C. K. & de Winther, M. P. J. Transcriptional and epigenetic regulation of macrophages in atherosclerosis. Nat. Rev. Cardiol. 17, 216–228 (2020). 4. Gauthier, B. R. et al. Thyroid hormones in diabetes, cancer, and aging. Aging Cell 19, e13260 (2020). 5. Pietrocola, F., Galluzzi, L., Bravo-San Pedro, J. M., Madeo, F. & Kroemer, G. Acetyl coenzyme A: a central metabolite and second messenger. Cell Metab. 21, 805–821 (2015).
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