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| Status |
Public on Mar 06, 2023 |
| Title |
Metabolic reprogramming by Acly inhibition using SB-204990 alters glucoregulation and modulates molecular mechanisms associated with aging |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
RNA from murine liver was extracted and hybridized on Affymetrix microarrays. We sought to obtain the transcriptional profile of liver tissue of mice fed a standard diet or a high fat diet treated or not with SB-204990
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| Web link |
https://www.nature.com/articles/s42003-023-04625-4
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| Contributor(s) |
Sola-García A, Cáliz-Molina MA, Villanueva IE, Petr M, Panadero-Morón C, González-Morán D, Martín-Vázquez ME, Narbona-Pérez ÁJ, López-Noriega L, Martínez-Corrales G, López-Fernández-Sobrino R, Carmona-Marin LM, Martínez-Force E, Yanes O, Vinaixa M, López-López D, Reyes JC, Dopazo J, Martín F, Gauthier BR, Scheibye-Knudsen M, Capilla-González V, Martín-Montalvo A |
| Citation(s) |
36890357 |
| Submission date |
Feb 16, 2022 |
| Last update date |
Jun 05, 2023 |
| Contact name |
Alejandro Martin-Montalvo |
| E-mail(s) |
alejandro.martinmontalvo@cabimer.es
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| Organization name |
CABIMER
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| Street address |
Av/ Américo Vespucio 24
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| City |
Seville |
| ZIP/Postal code |
41092 |
| Country |
Spain |
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| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA807590 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE196853_RAW.tar |
17.3 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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