Cargando…
UCHL1 Regulates Lipid and Perilipin 2 Level in Skeletal Muscle
Ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that was originally found in neurons. We found that UCHL1 is highly expressed in slow oxidative skeletal muscles, but its functions remain to be fully understood. In this study, we observed that UCHL1 protein levels in skeletal m...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021748/ https://www.ncbi.nlm.nih.gov/pubmed/35464088 http://dx.doi.org/10.3389/fphys.2022.855193 |
_version_ | 1784689902839922688 |
---|---|
author | Antony, Ryan Aby, Katherine Gao, Hongbo Eichholz, Mary Srinivasan, Rekha Li, Yifan |
author_facet | Antony, Ryan Aby, Katherine Gao, Hongbo Eichholz, Mary Srinivasan, Rekha Li, Yifan |
author_sort | Antony, Ryan |
collection | PubMed |
description | Ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that was originally found in neurons. We found that UCHL1 is highly expressed in slow oxidative skeletal muscles, but its functions remain to be fully understood. In this study, we observed that UCHL1 protein levels in skeletal muscle and C2C12 myotubes were downregulated by fasting or glucose starvation respectively. Skeletal muscle selective knockout (smKO) of UCHL1 resulted in a significant reduction of lipid content in skeletal muscle and improved glucose tolerance. UCHL1 smKO did not significantly change the levels of key proteins involved in oxidative metabolism such as SDHA, Akt, or PDH. Interestingly, while the levels of the major lipases and lipid transporters were unchanged, perilipin 2 was significantly downregulated in UCHL1 smKO muscle. Consistently, in C2C12 myotubes, UCHL1 siRNA knockdown also reduced perilipin 2 protein level. This data suggests that UCHL1 may stabilize perilipin 2 and thus lipid storage in skeletal muscle. |
format | Online Article Text |
id | pubmed-9021748 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90217482022-04-22 UCHL1 Regulates Lipid and Perilipin 2 Level in Skeletal Muscle Antony, Ryan Aby, Katherine Gao, Hongbo Eichholz, Mary Srinivasan, Rekha Li, Yifan Front Physiol Physiology Ubiquitin C-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that was originally found in neurons. We found that UCHL1 is highly expressed in slow oxidative skeletal muscles, but its functions remain to be fully understood. In this study, we observed that UCHL1 protein levels in skeletal muscle and C2C12 myotubes were downregulated by fasting or glucose starvation respectively. Skeletal muscle selective knockout (smKO) of UCHL1 resulted in a significant reduction of lipid content in skeletal muscle and improved glucose tolerance. UCHL1 smKO did not significantly change the levels of key proteins involved in oxidative metabolism such as SDHA, Akt, or PDH. Interestingly, while the levels of the major lipases and lipid transporters were unchanged, perilipin 2 was significantly downregulated in UCHL1 smKO muscle. Consistently, in C2C12 myotubes, UCHL1 siRNA knockdown also reduced perilipin 2 protein level. This data suggests that UCHL1 may stabilize perilipin 2 and thus lipid storage in skeletal muscle. Frontiers Media S.A. 2022-04-07 /pmc/articles/PMC9021748/ /pubmed/35464088 http://dx.doi.org/10.3389/fphys.2022.855193 Text en Copyright © 2022 Antony, Aby, Gao, Eichholz, Srinivasan and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Antony, Ryan Aby, Katherine Gao, Hongbo Eichholz, Mary Srinivasan, Rekha Li, Yifan UCHL1 Regulates Lipid and Perilipin 2 Level in Skeletal Muscle |
title | UCHL1 Regulates Lipid and Perilipin 2 Level in Skeletal Muscle |
title_full | UCHL1 Regulates Lipid and Perilipin 2 Level in Skeletal Muscle |
title_fullStr | UCHL1 Regulates Lipid and Perilipin 2 Level in Skeletal Muscle |
title_full_unstemmed | UCHL1 Regulates Lipid and Perilipin 2 Level in Skeletal Muscle |
title_short | UCHL1 Regulates Lipid and Perilipin 2 Level in Skeletal Muscle |
title_sort | uchl1 regulates lipid and perilipin 2 level in skeletal muscle |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021748/ https://www.ncbi.nlm.nih.gov/pubmed/35464088 http://dx.doi.org/10.3389/fphys.2022.855193 |
work_keys_str_mv | AT antonyryan uchl1regulateslipidandperilipin2levelinskeletalmuscle AT abykatherine uchl1regulateslipidandperilipin2levelinskeletalmuscle AT gaohongbo uchl1regulateslipidandperilipin2levelinskeletalmuscle AT eichholzmary uchl1regulateslipidandperilipin2levelinskeletalmuscle AT srinivasanrekha uchl1regulateslipidandperilipin2levelinskeletalmuscle AT liyifan uchl1regulateslipidandperilipin2levelinskeletalmuscle |