Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Schmid S

PROVIDER: S-EPMC9723918 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Schmid Svenia S Heim-Kupr Barbara B Pérez-Schindler Joaquín J Mansingh Shivani S Beer Markus M Mittal Nitish N Ehrenfeuchter Nikolaus N Handschin Christoph C

Molecular metabolism 20221116

<h4>Objective</h4>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.<h4>Methods</h4>We now have identified a role for the peroxisome proliferator-activa ...[more]

PMID: 36400401

Similar Datasets

Project description:BackgroundHypoxemia in humans may occur during high altitude mountaineering and in patients suffering from ventilatory insufficiencies such as cardiovascular- or respiratory disease including Chronic Obstructive Pulmonary Disease (COPD). In these conditions, hypoxemia has been correlated to reduced appetite and decreased food intake. Since hypoxemia and reduced food intake intersect in various physiological and pathological conditions and both induce loss of muscle mass, we investigated whether hypoxia aggravates fasting-induced skeletal muscle atrophy and evaluated underlying protein turnover signaling.MethodsMice were kept under hypoxic (8% oxygen) or normoxic conditions (21% oxygen), or were pair-fed to the hypoxia group for 12 days. Following an additional 24 hours of fasting, muscle weight and protein turnover signaling were assessed in the gastrocnemius muscle by RT-qPCR and Western blotting.ResultsLoss of gastrocnemius muscle mass in response to fasting in the hypoxic group was increased compared to the normoxic group, but not to the pair-fed normoxic control group. Conversely, the fasting-induced increase in poly-ubiquitin conjugation, and expression of the ubiquitin 26S-proteasome E3 ligases, autophagy-lysosomal degradation-related mRNA transcripts and proteins, and markers of the integrated stress response (ISR), were attenuated in the hypoxia group compared to the pair-fed group. Mammalian target of rapamycin complex 1 (mTORC1) downstream signaling was reduced by fasting under normoxic conditions, but sustained under hypoxic conditions. Activation of AMP-activated protein kinase (AMPK) / tuberous sclerosis complex 2 (TSC2) signaling by fasting was absent, in line with retained mTORC1 activity under hypoxic conditions. Similarly, hypoxia suppressed AMPK-mediated glucocorticoid receptor (GR) signaling following fasting, which corresponded with blunted proteolytic signaling responses.ConclusionsHypoxia aggravates fasting-induced muscle wasting, and suppresses AMPK and ISR activation. Altered AMPK-mediated regulation of mTORC1 and GR may underlie aberrant protein turnover signaling and affect muscle atrophy responses in hypoxic skeletal muscle.

Dataset Information

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

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets