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Metabolic reprogramming by Acly inhibition using SB-204990 alters glucoregulation and modulates molecular mechanisms associated with aging

  • Dades identificatives

    Identificador: imarina:9294231
    Autors:
    Sola-Garcia, AlejandroAngeles Caliz-Molina, MariaEspadas, IsabelPetr, MichaelPanadero-Moron, ConcepcionGonzalez-Moran, DanielEugenia Martin-Vazquez, MariaJesus Narbona-Perez, AlvaroLopez-Noriega, LiviaMartinez-Corrales, GuillermoLopez-Fernandez-Sobrino, RaulCarmona-Marin, Lina MMartinez-Force, EnriqueYanes, OscarVinaixa, MariaLopez-Lopez, DanielCarlos Reyes, JoseDopazo, JoaquinMartin, FranzGauthier, Benoit RScheibye-Knudsen, MortenCapilla-Gonzalez, VivianMartin-Montalvo, Alejandro
    Resum:
    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.
  • Altres:

    Autor segons l'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
    Departament: Enginyeria Electrònica, Elèctrica i Automàtica
    Autor/s de la URV: Vinaixa Crevillent, Maria / Yanes Torrado, Óscar
    Paraules clau: 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
    Resum: 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.
    Àrees temàtiques: 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)
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    Adreça de correu electrònic de l'autor: maria.vinaixa@urv.cat oscar.yanes@urv.cat maria.vinaixa@urv.cat
    Identificador de l'autor: 0000-0001-9804-0171 0000-0003-3695-7157 0000-0001-9804-0171
    Data d'alta del registre: 2024-10-12
    Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
    Enllaç font original: https://www.nature.com/articles/s42003-023-04625-4
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referència a l'article segons font original: Commun Biol. 6 (1): 250-
    Referència de l'ítem segons les normes 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
    DOI de l'article: 10.1038/s42003-023-04625-4
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2023
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Agricultural and Biological Sciences (Miscellaneous),Biochemistry, Genetics and Molecular Biology (Miscellaneous),Biology,Medicine (Miscellaneous)
    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
    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)
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