Muscle‐specific Perilipin2 down‐regulation affects lipid metabolism and induces myofiber hypertrophy
Abstract Background Perilipin2 (Plin2) belongs to a family of five highly conserved proteins, known for their role in lipid storage. Recent data indicate that Plin2 has an important function in cell metabolism and is involved in several human pathologies, including liver steatosis and Type II diabet...
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doaj-9c74979e204146b1a09ffbe960092d8b2020-11-25T00:19:17ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092019-02-011019511010.1002/jcsm.12355Muscle‐specific Perilipin2 down‐regulation affects lipid metabolism and induces myofiber hypertrophyMaria Conte0Andrea Armani1Giuseppe Conte2Andrea Serra3Claudio Franceschi4Marcello Mele5Marco Sandri6Stefano Salvioli7Department of Experimental, Diagnostic and Specialty Medicine (DIMES) University of Bologna Bologna ItalyVenetian Institute of Molecular Medicine (VIMM) Padova ItalyDepartment of Agriculture, Food and Environment University of Pisa Pisa ItalyDepartment of Agriculture, Food and Environment University of Pisa Pisa ItalyIRCCS Institute of Neurological Sciences of Bologna Bologna ItalyDepartment of Agriculture, Food and Environment University of Pisa Pisa ItalyVenetian Institute of Molecular Medicine (VIMM) Padova ItalyDepartment of Experimental, Diagnostic and Specialty Medicine (DIMES) University of Bologna Bologna ItalyAbstract Background Perilipin2 (Plin2) belongs to a family of five highly conserved proteins, known for their role in lipid storage. Recent data indicate that Plin2 has an important function in cell metabolism and is involved in several human pathologies, including liver steatosis and Type II diabetes. An association between Plin2 and lower muscle mass and strength has been found in elderly and inactive people, but its function in skeletal muscle is still unclear. Here, we addressed the role of Plin2 in adult muscle by gain and loss of function experiments. Methods By mean of in vivo Plin2 down‐regulation (shPlin2) and overexpression (overPlin2) in murine tibialis anterior muscle, we analysed the effects of Plin2 genetic manipulations on myofiber size and lipid composition. An analysis of skeletal muscle lipid composition was also performed in vastus lateralis samples from young and old patients undergoing hip surgery. Results We found that Plin2 down‐regulation was sufficient to induce a 30% increase of myofiber cross‐sectional area, independently of mTOR pathway. Alterations of lipid content and modulation of genes involved in lipid synthesis occurred in hypertrophic muscles. In particular, we showed a decrease of triglycerides, ceramides, and phosphatidylcoline:phosphatidylethanolamine ratio, a condition known to impact negatively on muscle function. Plin2 overexpression did not change fibre size; however, lipid composition was strongly affected in a way that is similar to that observed in human samples from old patients. Conclusions Altogether these data indicate that Plin2 is a critical mediator for the control of muscle mass, likely, but maybe not exclusively, through its critical role in the regulation of intracellular lipid content and composition.https://doi.org/10.1002/jcsm.12355Perilipin 2Lipid metabolismMuscle hypertrophyMuscle weaknessHuman ageing |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maria Conte Andrea Armani Giuseppe Conte Andrea Serra Claudio Franceschi Marcello Mele Marco Sandri Stefano Salvioli |
spellingShingle |
Maria Conte Andrea Armani Giuseppe Conte Andrea Serra Claudio Franceschi Marcello Mele Marco Sandri Stefano Salvioli Muscle‐specific Perilipin2 down‐regulation affects lipid metabolism and induces myofiber hypertrophy Journal of Cachexia, Sarcopenia and Muscle Perilipin 2 Lipid metabolism Muscle hypertrophy Muscle weakness Human ageing |
author_facet |
Maria Conte Andrea Armani Giuseppe Conte Andrea Serra Claudio Franceschi Marcello Mele Marco Sandri Stefano Salvioli |
author_sort |
Maria Conte |
title |
Muscle‐specific Perilipin2 down‐regulation affects lipid metabolism and induces myofiber hypertrophy |
title_short |
Muscle‐specific Perilipin2 down‐regulation affects lipid metabolism and induces myofiber hypertrophy |
title_full |
Muscle‐specific Perilipin2 down‐regulation affects lipid metabolism and induces myofiber hypertrophy |
title_fullStr |
Muscle‐specific Perilipin2 down‐regulation affects lipid metabolism and induces myofiber hypertrophy |
title_full_unstemmed |
Muscle‐specific Perilipin2 down‐regulation affects lipid metabolism and induces myofiber hypertrophy |
title_sort |
muscle‐specific perilipin2 down‐regulation affects lipid metabolism and induces myofiber hypertrophy |
publisher |
Wiley |
series |
Journal of Cachexia, Sarcopenia and Muscle |
issn |
2190-5991 2190-6009 |
publishDate |
2019-02-01 |
description |
Abstract Background Perilipin2 (Plin2) belongs to a family of five highly conserved proteins, known for their role in lipid storage. Recent data indicate that Plin2 has an important function in cell metabolism and is involved in several human pathologies, including liver steatosis and Type II diabetes. An association between Plin2 and lower muscle mass and strength has been found in elderly and inactive people, but its function in skeletal muscle is still unclear. Here, we addressed the role of Plin2 in adult muscle by gain and loss of function experiments. Methods By mean of in vivo Plin2 down‐regulation (shPlin2) and overexpression (overPlin2) in murine tibialis anterior muscle, we analysed the effects of Plin2 genetic manipulations on myofiber size and lipid composition. An analysis of skeletal muscle lipid composition was also performed in vastus lateralis samples from young and old patients undergoing hip surgery. Results We found that Plin2 down‐regulation was sufficient to induce a 30% increase of myofiber cross‐sectional area, independently of mTOR pathway. Alterations of lipid content and modulation of genes involved in lipid synthesis occurred in hypertrophic muscles. In particular, we showed a decrease of triglycerides, ceramides, and phosphatidylcoline:phosphatidylethanolamine ratio, a condition known to impact negatively on muscle function. Plin2 overexpression did not change fibre size; however, lipid composition was strongly affected in a way that is similar to that observed in human samples from old patients. Conclusions Altogether these data indicate that Plin2 is a critical mediator for the control of muscle mass, likely, but maybe not exclusively, through its critical role in the regulation of intracellular lipid content and composition. |
topic |
Perilipin 2 Lipid metabolism Muscle hypertrophy Muscle weakness Human ageing |
url |
https://doi.org/10.1002/jcsm.12355 |
work_keys_str_mv |
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