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| Status |
Public on Jul 17, 2023 |
| Title |
ER-associated degradation maintains postnatal muscle hypertophy and systemic energy metabolism |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The growth of skeletal muscle relies on a delicate equilibrium between protein synthesis and degradation; however, how proteostasis is managed in the endoplasmic reticulum is largely unknown. Here, we report that the SEL1L-HRD1 endoplasmic reticulum (ER)-associated degradation (ERAD) complex, the primary molecular machinery that degrades misfolded proteins in the ER, is vital to maintain postnatal muscle growth and systemic energy balance. Myocyte-specific SEL1L deletion blunts the hypertrophic phase of muscle growth, resulting in a net zero gain of muscle mass during this developmental period and significant reduction in overall body growth. In addition, myocyte-specific SEL1L deletion triggered a systemic reprogramming of metabolism characterized by improved glucose sensitivity, enhanced beiging of adipocytes, and resistance to diet induced obesity. These effects were partially mediated by the upregulation of the myokine FGF21. These findings highlight the pivotal role of SEL1L-HRD1 ERAD activity in skeletal myocytes for postnatal muscle growth, and its physiological integration in maintaining whole-body energy balance.
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| Overall design |
Gene expression was profiled in gastrocnemius muscle isolated from 8-week-old wildtype and muscle-specific Sel1L-deficient mice.
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| Contributor(s) |
Abdon B, Liang Y, da Luz Scheffer D, Torres M, Shrestha N, Reinert RB, Lu Y, Pederson B, Bugarin-Lapuz A, Kersten S, Qi L |
| Citation missing |
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| Submission date |
Jul 12, 2023 |
| Last update date |
Jul 17, 2023 |
| Contact name |
Guido Hooiveld |
| E-mail(s) |
guido.hooiveld@wur.nl
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| Organization name |
Wageningen University
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| Department |
Div. Human Nutrition & Health
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| Lab |
Nutrition, Metabolism & Genomics Group
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| Street address |
HELIX, Stippeneng 4
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| City |
Wageningen |
| ZIP/Postal code |
NL-6708WE |
| Country |
Netherlands |
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| Platforms (1) |
| GPL17400 |
[MoGene-2_1-st] Affymetrix Mouse Gene 2.1 ST Array [transcript (gene) version] |
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| Samples (6)
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| GSM7596747 |
gastrocnemius muscle, isolated from wildtype mouse, replicate 1 |
| GSM7596748 |
gastrocnemius muscle, isolated from wildtype mouse, replicate 2 |
| GSM7596749 |
gastrocnemius muscle, isolated from wildtype mouse, replicate 3 |
| GSM7596750 |
gastrocnemius muscle, isolated from muscle-specific Sel1L-deficient mouse, replicate 1 |
| GSM7596751 |
gastrocnemius muscle, isolated from muscle-specific Sel1L-deficient mouse, replicate 2 |
| GSM7596752 |
gastrocnemius muscle, isolated from muscle-specific Sel1L-deficient mouse, replicate 3 |
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| Relations |
| BioProject |
PRJNA994154 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE237194_RAW.tar |
27.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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