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PGC-1β modulates catabolism and fiber atrophy in the fasting-response of specific skeletal muscle beds

OBJECTIVE: Skeletal muscle is a pivotal organ for the coordination of systemic metabolism, constituting one of the largest storage site for glucose, lipids and amino acids. Tight temporal orchestration of protein breakdown in times of fasting has to be balanced with preservation of muscle mass and f...

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Autores principales: Schmid, Svenia, Heim-Kupr, Barbara, Pérez-Schindler, Joaquín, Mansingh, Shivani, Beer, Markus, Mittal, Nitish, Ehrenfeuchter, Nikolaus, Handschin, Christoph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9723918/
https://www.ncbi.nlm.nih.gov/pubmed/36400401
http://dx.doi.org/10.1016/j.molmet.2022.101643
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author Schmid, Svenia
Heim-Kupr, Barbara
Pérez-Schindler, Joaquín
Mansingh, Shivani
Beer, Markus
Mittal, Nitish
Ehrenfeuchter, Nikolaus
Handschin, Christoph
author_facet Schmid, Svenia
Heim-Kupr, Barbara
Pérez-Schindler, Joaquín
Mansingh, Shivani
Beer, Markus
Mittal, Nitish
Ehrenfeuchter, Nikolaus
Handschin, Christoph
author_sort Schmid, Svenia
collection PubMed
description OBJECTIVE: Skeletal muscle is a pivotal organ for the coordination of systemic metabolism, constituting one of the largest storage site for glucose, lipids and amino acids. Tight temporal orchestration of protein breakdown in times of fasting has to be balanced with preservation of muscle mass and function. However, the molecular mechanisms that control the fasting response in muscle are poorly understood. METHODS: We now have identified a role for the peroxisome proliferator-activated receptor γ coactivator 1β (PGC-1β) in the regulation of catabolic pathways in this context in muscle-specific loss-of-function mouse models. RESULTS: Muscle-specific knockouts for PGC-1β experience mitigated muscle atrophy in fasting, linked to reduced expression of myostatin, atrogenes, activation of AMP-dependent protein kinase (AMPK) and other energy deprivation signaling pathways. At least in part, the muscle fasting response is modulated by a negative effect of PGC-1β on the nuclear factor of activated T-cells 1 (NFATC1). CONCLUSIONS: Collectively, these data highlight the complex regulation of muscle metabolism and reveal a new role for muscle PGC-1β in the control of proteostasis in fasting.
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spelling pubmed-97239182022-12-07 PGC-1β modulates catabolism and fiber atrophy in the fasting-response of specific skeletal muscle beds Schmid, Svenia Heim-Kupr, Barbara Pérez-Schindler, Joaquín Mansingh, Shivani Beer, Markus Mittal, Nitish Ehrenfeuchter, Nikolaus Handschin, Christoph Mol Metab Original Article OBJECTIVE: Skeletal muscle is a pivotal organ for the coordination of systemic metabolism, constituting one of the largest storage site for glucose, lipids and amino acids. Tight temporal orchestration of protein breakdown in times of fasting has to be balanced with preservation of muscle mass and function. However, the molecular mechanisms that control the fasting response in muscle are poorly understood. METHODS: We now have identified a role for the peroxisome proliferator-activated receptor γ coactivator 1β (PGC-1β) in the regulation of catabolic pathways in this context in muscle-specific loss-of-function mouse models. RESULTS: Muscle-specific knockouts for PGC-1β experience mitigated muscle atrophy in fasting, linked to reduced expression of myostatin, atrogenes, activation of AMP-dependent protein kinase (AMPK) and other energy deprivation signaling pathways. At least in part, the muscle fasting response is modulated by a negative effect of PGC-1β on the nuclear factor of activated T-cells 1 (NFATC1). CONCLUSIONS: Collectively, these data highlight the complex regulation of muscle metabolism and reveal a new role for muscle PGC-1β in the control of proteostasis in fasting. Elsevier 2022-11-16 /pmc/articles/PMC9723918/ /pubmed/36400401 http://dx.doi.org/10.1016/j.molmet.2022.101643 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Article
Schmid, Svenia
Heim-Kupr, Barbara
Pérez-Schindler, Joaquín
Mansingh, Shivani
Beer, Markus
Mittal, Nitish
Ehrenfeuchter, Nikolaus
Handschin, Christoph
PGC-1β modulates catabolism and fiber atrophy in the fasting-response of specific skeletal muscle beds
title PGC-1β modulates catabolism and fiber atrophy in the fasting-response of specific skeletal muscle beds
title_full PGC-1β modulates catabolism and fiber atrophy in the fasting-response of specific skeletal muscle beds
title_fullStr PGC-1β modulates catabolism and fiber atrophy in the fasting-response of specific skeletal muscle beds
title_full_unstemmed PGC-1β modulates catabolism and fiber atrophy in the fasting-response of specific skeletal muscle beds
title_short PGC-1β modulates catabolism and fiber atrophy in the fasting-response of specific skeletal muscle beds
title_sort pgc-1β modulates catabolism and fiber atrophy in the fasting-response of specific skeletal muscle beds
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9723918/
https://www.ncbi.nlm.nih.gov/pubmed/36400401
http://dx.doi.org/10.1016/j.molmet.2022.101643
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