Author, as appears in the article.: Sola-Garcia, Alejandro; Angeles Caliz-Molina, Maria; Espadas, Isabel; Petr, Michael; Panadero-Moron, Concepcion; Gonzalez-Moran, Daniel; Eugenia Martin-Vazquez, Maria; Jesus Narbona-Perez, Alvaro; Lopez-Noriega, Livia; Martinez-Corrales, Guillermo; Lopez-Fernandez-Sobrino, Raul; Carmona-Marin, Lina M; Martinez-Force, Enrique; Yanes, Oscar; Vinaixa, Maria; Lopez-Lopez, Daniel; Carlos Reyes, Jose; Dopazo, Joaquin; Martin, Franz; Gauthier, Benoit R; Scheibye-Knudsen, Morten; Capilla-Gonzalez, Vivian; Martin-Montalvo, Alejandro
Department: Enginyeria Electrònica, Elèctrica i Automàtica
URV's Author/s: Vinaixa Crevillent, Maria / Yanes Torrado, Óscar
Keywords: Mice Lipid metabolism Diet, high-fat Atp-citrate-lyase Atp citrate (pro-s)-lyase Animals Aging rapamycin mass-spectrometry identification high-fat diet extends life-span expression enzyme-activities bempedoic acid adipose-tissue
Abstract: ATP-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.
Thematic Areas: Medicine (miscellaneous) General biochemistry,genetics and molecular biology General agricultural and biological sciences Biology Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all) Agricultural and biological sciences (miscellaneous) Agricultural and biological sciences (all)
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: maria.vinaixa@urv.cat oscar.yanes@urv.cat maria.vinaixa@urv.cat
Author identifier: 0000-0001-9804-0171 0000-0003-3695-7157 0000-0001-9804-0171
Record's date: 2024-10-12
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.nature.com/articles/s42003-023-04625-4
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Commun Biol. 6 (1): 250-
APA: Sola-Garcia, Alejandro; Angeles Caliz-Molina, Maria; Espadas, Isabel; Petr, Michael; Panadero-Moron, Concepcion; Gonzalez-Moran, Daniel; Eugenia Marti (2023). Metabolic reprogramming by Acly inhibition using SB-204990 alters glucoregulation and modulates molecular mechanisms associated with aging. Commun Biol, 6(1), 250-. DOI: 10.1038/s42003-023-04625-4
Article's DOI: 10.1038/s42003-023-04625-4
Entity: Universitat Rovira i Virgili
Journal publication year: 2023
Publication Type: Journal Publications