Biogerontology

, Volume 16, Issue 3, pp 329–340 | Cite as

Differential expression of perilipin 2 and 5 in human skeletal muscle during aging and their association with atrophy-related genes

  • Maria Conte
  • Francesco Vasuri
  • Enrico Bertaggia
  • Andrea Armani
  • Aurelia Santoro
  • Elena Bellavista
  • Alessio Degiovanni
  • Antonia D’Errico-Grigioni
  • Giovanni Trisolino
  • Miriam Capri
  • Martino V. Franchi
  • Marco V. Narici
  • Marco Sandri
  • Claudio Franceschi
  • Stefano Salvioli
Research Article

Abstract

Sarcopenia, the progressive loss of muscle mass and strength, is a phenomenon characterizing human aging whose etiology is still not clear. While there is increasing evidence for the influence of inter-muscular adipose tissue infiltration in the development of sarcopenia, much less is known about a possible role for intra-muscular triglycerides (IMTG). IMTG accumulate in form of lipid droplets decorated by proteins such as Perilipins (Plins). In skeletal muscle the most abundant are Plin2 and Plin5. In this study we compared the expression of these two Plins in Vastus lateralis muscle samples of subjects of different age, both healthy donors (HD) and patients with limited lower limb mobility (LLMI). These latter are characterized by a condition of chronic physical inactivity. Plin2 expression resulted higher in old age for both HD and LLMI patients, while Plin5 slightly decreased only in LLMI patients. Moreover, in these patients, only Plin2 was associated with the decrease of muscle strength and the expression of factors related to muscle atrophy (MuRF1, Atrogin and p53). An increase in Plin2 and a concomitant decrease of Plin5 was also observed when we considered animal model of disuse-induced muscle atrophy. As a whole, these data indicate that Plin2 and Plin5 have a different expression pattern during muscle aging and inactivity, and only Plin2 appears to be associated with functional alterations of the muscle.

Keywords

Muscle aging Sarcopenia Perilipins Atrophy p53 

Notes

Acknowledgments

The research leading to these results has received funding from the European Union’s Seventh Framework Programme (FP7/2007-2011) under Grant agreement No. 223576 (MYOAGE) to CF, MN and MS.

Conflict of interests

The authors declare no conflict of interests.

References

  1. Aon MA, Bhatt N, Cortassa SC (2014) Mitochondrial and cellular mechanisms for managing lipid excess. Front Physiol 5:282. doi: 10.3389/fphys.2014.00282 CrossRefPubMedCentralPubMedGoogle Scholar
  2. Bickel PE, Tansey JT, Welte MA (2009) PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores. Biochim Biophys Acta 1791:419–440. doi: 10.1016/j.bbalip.2009.04.002 CrossRefPubMedCentralPubMedGoogle Scholar
  3. Bosma M, Hesselink MK, Sparks LM, Timmers S, Ferraz MJ, Mattijssen F, van Beurden D, Schaart G, de Baets MH, Verheyen FK, Kersten S, Schrauwen P (2012a) Perilipin 2 improves insulin sensitivity in skeletal muscle despite elevated intramuscular lipid levels. Diabetes 61:2679–2690. doi: 10.2337/db11-1402 CrossRefPubMedCentralPubMedGoogle Scholar
  4. Bosma M, Minnaard R, Sparks LM, Schaart G, Losen M, de Baets MH, Duimel H, Kersten S, Bickel PE, Schrauwen P, Hesselink MK (2012b) The lipid droplet coat protein perilipin 5 also localizes to muscle mitochondria. Histochem Cell Biol 137:205–216. doi: 10.1007/s00418-011-0888-x CrossRefPubMedCentralPubMedGoogle Scholar
  5. Bosma M, Sparks LM, Hooiveld GJ, Jorgensen JA, Houten SM, Schrauwen P, Kersten S, Hesselink MK (2013) Overexpression of PLIN5 in skeletal muscle promotes oxidative gene expression and intramyocellular lipid content without compromising insulin sensitivity. Biochim Biophys Acta 1831:844–852. doi: 10.1016/j.bbalip.2013.01.007 CrossRefPubMedGoogle Scholar
  6. Breen L, Phillips SM (2013) Interactions between exercise and nutrition to prevent muscle waste during aging. Br J Clin Pharmacol 75:708–715. doi: 10.1111/j.1365-2125.2012.04456.x PubMedCentralPubMedGoogle Scholar
  7. Conte M, Vasuri F, Trisolino G, Bellavista E, Santoro A, Degiovanni A, Martucci E, D’Errico Grigioni A, Caporossi D, Capri M, Maier AB, Seynnes O, Barberi L, Musarò A, Narici MV, Franceschi C, Salvioli S (2013) Increased Plin2 expression in human skeletal muscle is associated with sarcopenia and muscle weakness. PLoS One 8:e73709. doi: 10.1371/journal.pone.0073709 CrossRefPubMedCentralPubMedGoogle Scholar
  8. Corcoran MP, Lamon-Fava S, Fielding RA (2007) Skeletal muscle lipid deposition and insulin resistance: effect of dietary fatty acids and exercise. Am J Clin Nutr 85:662–677PubMedGoogle Scholar
  9. Crane JD, Devries MC, Safdar A, Hamadeh MJ, Tarnopolsky MA (2010) The effect of aging on human skeletal muscle mitochondrial and intramyocellular lipid ultrastructure. J Gerontol A Biol Sci Med Sci 65:119–128. doi: 10.1093/gerona/glp179 CrossRefPubMedGoogle Scholar
  10. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinková E, Vandewoude M, Zamboni M (2010) European Working Group on Sarcopenia in Older People. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing 39:412–423. doi: 10.1093/ageing/afq034 CrossRefPubMedCentralPubMedGoogle Scholar
  11. Farese RV Jr, Walther TC (2009) Lipid droplets finally get a little RESPECT. Cell 139:855–860Google Scholar
  12. Derdak Z, Villegas KA, Harb R, Wu AM, Sousa A, Wands JR (2013) Inhibition of p53 attenuates steatosis and liver injury in a mouse model of non-alcoholic fatty liver disease. J Hepatol 58:785–791. doi: 10.1016/j.jhep.2012.11.042 CrossRefPubMedCentralPubMedGoogle Scholar
  13. Fox DK, Ebert SM, Bongers KS, Dyle MC, Bullard SA, Dierdorff JM, Kunkel SD, Adams CM (2014) p53 and ATF4 mediate distinct and additive pathways to skeletal muscle atrophy during limb immobilization. Am J Physiol Endocrinol Metab 307:E245–E261. doi: 10.1152/ajpendo.00010.2014 CrossRefPubMedGoogle Scholar
  14. Goodpaster BH, He J, Watkins S, Kelley DE (2001) Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J Clin Endocrinol Metab 86:5755–5761CrossRefPubMedGoogle Scholar
  15. Gori M, Barbaro B, Arciello M, Maggio R, Viscomi C, Longo A, Balsano C (2014) Protective effect of the Y220C mutant p53 against steatosis: good news? J Cell Physiol 229:1182–1192. doi: 10.1002/jcp.24550 CrossRefPubMedGoogle Scholar
  16. Gumucio JP, Mendias CL (2013) Atrogin-1, MuRF-1, and sarcopenia. Endocrine 43:12–21. doi: 10.1007/s12020-012-9751-7 CrossRefPubMedCentralPubMedGoogle Scholar
  17. Heilbronn L, Smith SR, Ravussin E (2004) Failure of fat cell proliferation, mitochondrial function and fat oxidation results in ectopic fat storage, insulin resistance and type II diabetes mellitus. Int J Obes Relat Metab Disord. 28 Suppl 4:S12-S21Google Scholar
  18. Johannsen DL, Conley KE, Bajpeyi S, Punyanitya M, Gallagher D, Zhang Z, Covington J, Smith SR, Ravussin E (2012) Ectopic lipid accumulation and reduced glucose tolerance in elderly adults are accompanied by altered skeletal muscle mitochondrial activity. J Clin Endocrinol Metab 97:242–250. doi: 10.1210/jc.2011-1798 CrossRefPubMedCentralPubMedGoogle Scholar
  19. Kimmel AR, Brasaemle DL, McAndrews-Hill M, Sztalryd C, Londos C (2010) Adoption of PERILIPIN as a unifying nomenclature for the mammalian PAT-family of intracellular lipid storage droplet proteins. J Lipid Res 51:468–471. doi: 10.1194/jlr.R000034 CrossRefPubMedCentralPubMedGoogle Scholar
  20. Konopka AR, Sreekumaran Nair K (2013) Mitochondrial and skeletal muscle health with advancing age. Mol Cell Endocrinol 379:19–29Google Scholar
  21. Macpherson RE, Vandenboom R, Roy BD, Peters SJ (2013) Skeletal muscle PLIN3 and PLIN5 are serine phosphorylated at rest and following lipolysis during adrenergic or contractile stimulation. Physiol Rep 1:e00084. doi: 10.1002/phy2.84 CrossRefPubMedCentralPubMedGoogle Scholar
  22. Marcus RL, Addison O, LaStayo PC (2013) Intramuscular adipose tissue attenuates gains in muscle quality in older adults at high risk for falling. A brief report. J Nutr Health Aging 17:215–218. doi: 10.1007/s12603-012-0377-5 CrossRefPubMedGoogle Scholar
  23. Narici MV, Maffulli N (2010) Sarcopenia: characteristics, mechanisms and functional significance. Br Med Bull 95:139–159. doi: 10.1093/bmb/ldq008 CrossRefPubMedGoogle Scholar
  24. Pfaffl MW (2004) Quantification strategies in real-time PCR. In: Bustin SA (ed) A–Z of quantitative PCR., Biotechnology seriesInternational University Line (IUL), La Jolla, pp 87–120Google Scholar
  25. Pol A, Gross SP, Parton RG (2014) Review: biogenesis of the multifunctional lipid droplet: lipids, proteins, and sites. J Cell Biol 204:635–646. doi: 10.1083/jcb.201311051 CrossRefPubMedCentralPubMedGoogle Scholar
  26. Sandri M (2008) Signaling in muscle atrophy and hypertrophy. Physiology (Bethesda) 23:160–170. doi: 10.1152/physiol.00041.2007 CrossRefGoogle Scholar
  27. Sandri M, Lin J, Handschin C, Yang W, Arany ZP, Lecker SH, Goldberg AL, Spiegelman BM (2006) PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription. Proc Natl Acad Sci USA 103:16260–16265CrossRefPubMedCentralPubMedGoogle Scholar
  28. Sandri M, Barberi L, Bijlsma AY, Blaauw B, Dyar KA, Milan G, Mammucari C, Meskers CG, Pallafacchina G, Paoli A, Pion D, Roceri M, Romanello V, Serrano AL, Toniolo L, Larsson L, Maier AB, Muñoz-Cánoves P, Musarò A, Pende M, Reggiani C, Rizzuto R, Schiaffino S (2013) Signalling pathways regulating muscle mass in ageing skeletal muscle: the role of the IGF1-Akt-mTOR-FoxO pathway. Biogerontology 14:303–323. doi: 10.1007/s10522-013-9432-9 CrossRefPubMedGoogle Scholar
  29. Schwarzkopf M, Coletti D, Marazzi G, Sassoon D (2008) Chronic p53 activity leads to skeletal muscle atrophy and muscle stem cell perturbation. Basic Appl Myol 18:131–138Google Scholar
  30. Tardif N, Salles J, Guillet C, Tordjman J, Reggio S, Landrier JF, Giraudet C, Patrac V, Bertrand-Michel J, Migne C, Collin ML, Chardigny JM, Boirie Y, Walrand S (2014) Muscle ectopic fat deposition contributes to anabolic resistance in obese sarcopenic old rats through eIF2α activation. Aging Cell. doi: 10.1111/acel.12263 PubMed PMID: 25139155PubMedCentralPubMedGoogle Scholar
  31. Watt MJ, Hoy AJ (2012) Lipid metamolism in skeletal muscle: generation and maladaptive intracellular signals for cellular function. Am J Physiol Endocrinol Metab 302:E1315–E1328. doi: 10.1152/ajpendo.00561.2011 CrossRefPubMedGoogle Scholar
  32. Wolins NE, Brasaemle DL, Bickel PE (2006) A proposed model of fat packaging by exchangeable lipid droplet proteins. FEBS Lett 580:5484–5491CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Maria Conte
    • 1
  • Francesco Vasuri
    • 2
  • Enrico Bertaggia
    • 3
    • 4
  • Andrea Armani
    • 3
    • 4
  • Aurelia Santoro
    • 1
  • Elena Bellavista
    • 1
  • Alessio Degiovanni
    • 2
  • Antonia D’Errico-Grigioni
    • 2
  • Giovanni Trisolino
    • 5
  • Miriam Capri
    • 1
  • Martino V. Franchi
    • 6
  • Marco V. Narici
    • 6
  • Marco Sandri
    • 3
    • 4
    • 7
  • Claudio Franceschi
    • 1
  • Stefano Salvioli
    • 1
  1. 1.Department of Experimental, Diagnostic and Specialty Medicine and Interdepartmental Centre “L. Galvani” (CIG)University of BolognaBolognaItaly
  2. 2.Department of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi Hospital, “F. Addarii” Institute of Oncology and Transplant PathologyUniversity of BolognaBolognaItaly
  3. 3.Venetian Institute of Molecular MedicineUniversity of PadovaPaduaItaly
  4. 4.Department of Biomedical ScienceUniversity of PadovaPaduaItaly
  5. 5.Reconstructive Hip and Knee Joint SurgeryIstituto Ortopedico RizzoliBolognaItaly
  6. 6.Division of Clinical Physiology, School of Graduate Entry Medicine and Health, Derby Royal HospitalUniversity of NottinghamDerbyUK
  7. 7.Telethon Institute of Genetics and MedicinePozzuoliItaly

Personalised recommendations