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| Hauptverfasser: | , , , , , , , , |
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| Format: | Recurso digital |
| Sprache: | Englisch |
| Veröffentlicht: |
Zenodo
2022
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| Schlagworte: | |
| Online-Zugang: | https://doi.org/10.5281/zenodo.7215980 |
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Inhaltsangabe:
- <p>Dietary sulfur amino acid (SAA) restriction (SAAR) protects against diet-induced obesity, extends healthspan and coincides with an overall reduction in hepatic protein synthesis. To explore the underpinnings of SAAR-induced slowed growth and its benefits on proteostasis control, we resolved changes in hepatic mRNA and protein abundances and compared synthesis rates of 820 individual liver proteins. To achieve this, adult male mice were provided deuterium-labeled drinking water while freely consuming either a regular-fat or high fat diet that was restricted in SAA. Livers from these mice and their respective dietary controls were used to conduct transcriptomic, proteomic, and kinetic proteomic analyses. We found that remodeling of the transcriptome by SAAR was largely agnostic to dietary fat content. Shared signatures included activation of the integrated stress response alongside alterations in metabolic processes impacting lipids, fatty acids, and amino acids. Changes to the proteome correlated poorly with the transcriptome and yet, functional clustering of kinetic proteomic changes in liver during SAAR revealed that management of fatty acids and amino acids were altered to support central metabolism and redox balance. Dietary SAAR also strongly influenced the synthesis rates of ribosomal proteins and ribosome-interacting proteins regardless of dietary fat. Taken together, dietary SAAR alters the transcriptome and kinetic proteome in liver to safely manage increased fatty acid flux and energy use, and couples this with targeted changes in the ribo-interactome to support proteostasis and slowed growth.</p>