Human skeletal muscle perilipin 2 and 3 expression varies with insulin sensitivity

Abstract

Background: Impaired insulin sensitivity may partly arise from a dysregulated lipid metabolism in human skeletal muscle. This study investigates the expression levels of perilipin 2, 3, and 5, and four key lipases in human skeletal muscle from the subjects that exhibit a range from normal to very low insulin sensitivity. Methods: 25 middle aged male participants were matched for lean body mass and recruited into three groups; type 2 diabetes patients (T2D), impaired glucose tolerance (IGT), and healthy sedentary controls (CON) according to their glucose tolerance and VO2peak. A muscle biopsy was obtained from vastus lateralis, and a two-step sequential euglycaemic-hyperinsulinaemic clamp was performed. Muscle samples were analyzed by Western blot for expression of perilipin 2, 3, 5, adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), endothelial lipase (EL) and lipoprotein lipase (LPL). Results: Perilipin 3 expression was higher in T2D compared to CON. Perilipin 2 expression was higher in CON than T2D. We observed no difference in expression of perili pin 5, ATGL, HSL, EL or LPL between the groups. Conclusions: In the present study the muscle perilipin 3 expression and perilipin 2 expression varied markedly with insulin sensitivity. This difference in perilipin expression may indicate that the lipid droplet function and thus storage and release of fatty acid-vary with insulin sensitivity.

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Vigelsø, A. , Prats, C. , Ploug, T. , Dela, F. and Helge, J. (2013) Human skeletal muscle perilipin 2 and 3 expression varies with insulin sensitivity. Journal of Biomedical Science and Engineering, 6, 65-72. doi: 10.4236/jbise.2013.65A010.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Bartz, R., Li, W.H., Venables, B., Zehmer, J.K., Roth, M.R., Welti, R., Anderson, R.G., Liu, P. and Chapman, K.D. (2007) Lipidomics reveals that adiposomes store ether lipids and mediate phospholipid traffic. The Journal of Lipid Research, 48, 837-847. doi:10.1194/jlr.M600413-JLR200
[2] Kimmel, A.R., Brasaemle, D.L., McAndrews-Hill, M., Sztalryd, C. and Londos, C. (2010) Adoption of PERILIPIN as a unifying nomenclature for the mammalian PATfamily of intracellular lipid storage droplet proteins. The Journal of Lipid Research, 51, 468-471. doi:10.1194/jlr.R000034
[3] Brasaemle, D.L., Dolios, G., Shapiro, L. and Wang, R. (2004) Proteomic analysis of proteins associated with lipid droplets of basal and lipolytically stimulated 3T3-L1 adipocytes. Journal of Biological Chemistry, 279, 4683546842. doi:10.1074/jbc.M409340200
[4] Alsted, T.J., Nybo, L., Schweiger, M., Fledelius, C., Jacobsen, P., Zimmermann, R., Zechner, R. and Kiens, B. (2009) Adipose triglyceride lipase in human skeletal muscle is upregulated by exercise training. American Journal of Physiology—Endocrinology and Metabolism, 296, E445-E453. doi:10.1152/ajpendo.90912.2008
[5] Lampidonis, A.D., Rogdakis, E., Voutsinas, G.E. and Stravopodis, D.J. (2011) The resurgence of HormoneSensitive Lipase (HSL) in mammalian lipolysis. Gene, 477, 1-11. doi:10.1016/j.gene.2011.01.007
[6] Schweiger, M, Schoiswohl, G., Lass, A., Radner, F.P., Haemmerle, G., Malli, R., Graier, W., Cornaciu, I., Oberer, M., Salvayre, R., Fischer, J., Zechner, R. and Zimmermann, R. (2008) The C-terminal region of human adipose triglyceride lipase affects enzyme activity and lipid droplet binding. The Journal of Biological Chemistry, 283, 17211-17220. doi:10.1074/jbc.M710566200
[7] Pan, D.A., Lillioja, S., Kriketos, A.D., Milner, M.R., Baur, L.A., Bogardus, C., Jenkins, A.B. and Storlien, L.H. (1997) Skeletal muscle triglyceride levels are inversely related to insulin action. Diabetes, 46, 983-988. doi:10.2337/diabetes.46.6.983
[8] Goodpaster, B.H., He, J., Watkins, S. and Kelley, D.E. (2001) Skeletal muscle lipid content and insulin resistance: Evidence for a paradox in endurance-trained athletes. The Journal of Clinical Endocrinology & Metabolism, 86, 5755-5761. doi:10.1210/jc.86.12.5755
[9] Unger, R.H. (2002) Lipotoxic diseases. Annual Review of Medicine, 53, 319-336. doi:10.1146/annurev.med.53.082901.104057
[10] Summers, S.A. (2006) Ceramides in insulin resistance and lipotoxicity. Progress in Lipid Research, 45, 42-72. doi:10.1016/j.plipres.2005.11.002
[11] Koves, T.R., Ussher, J.R., Noland, R.C., Slentz, D., Mosedale, M., Ilkayeva, O., Bain, J., Stevens, R., Dyck, J.R., Newgard, C.B., Lopaschuk, G.D. and Muoio, D.M. (2008) Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metabolism, 7, 45-56. doi:10.1016/j.cmet.2007.10.013
[12] Phillips, S A, Choe, C.C., Ciaraldi, T.P., Greenberg, A.S., Kong, A.P.S., Baxi, S.C., Christiansen, L., Mudaliar, S.R. and Henry, R.R. (2005) Adipocyte differentiation-related protein in human skeletal muscle: Relationship to insulin sensitivity[ast][ast]. North American Association for the Study of Obesity (NAASO), 8, 1321-1329.
[13] Shaw, C.S., Shepherd, S.O., Wagenmakers, A.J., Hansen, D., Dendale, P. and van Loon, L.J. (2012) Prolonged exercise training increases intramuscular lipid content and perilipin 2 expression in type I muscle fibres of patients with type 2 diabetes. American Journal of Physiology— Endocrinology and Metabolism, 303, E1158-E1165. doi:10.1152/ajpendo.00272.2012
[14] Minnaard, R., Schrauwen, P., Schaart, G., Jorgensen, J.A., Lenaers, E., Mensink, M. and Hesselink, M.K. (2009) Adipocyte differentiation-related protein and OXPAT in rat and human skeletal muscle: Involvement in lipid accumulation and type 2 diabetes mellitus. The Journal of Clinical Endocrinology & Metabolism, 94, 4077-4085. doi:10.1210/jc.2009-0352
[15] Skov-Jensen, C., Skovbro, M., Flint, A., Helge, J.W. and Dela, F. (2007) Contraction-mediated glucose uptake is increased in men with impaired glucose tolerance. Applied Physiology, Nutrition, and Metabolism, 32, 115124. doi:10.1139/h06-098
[16] Skovbro, M., Baranowski, M., Skov-Jensen, C., Flint, A., Dela, F., Gorski, J. and Helge, J.W. (2008) Human skeletal muscle ceramide content is not a major factor in muscle insulin sensitivity. Applied Physiology, Nutrition, and Metabolism, 7, 1253-1260.
[17] Bergstrom, J. (1975) Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scandinavian Journal of Clinical & Laboratory Investigation, 35, 609-616. doi:10.3109/00365517509095787
[18] Son, S.H., Goo, Y.H., Chang, B.H. and Paul, A. (2012) Perilipin 2 (PLIN2)-deficiency does not increase cholesterol-induced toxicity in macrophages. PLoS ONE, 7, e33063. doi:10.1371/journal.pone.0033063
[19] Kirpich, I.A., Gobejishvili, L.N., Bon, H.M., Waigel, S., Cave, M., Arteel, G., Barve, S.S., McClain, C.J. and Deaciuc, I.V. (2011) Integrated hepatic transcriptome and proteome analysis of mice with high-fat diet-induced nonalcoholic fatty liver disease. The Journal of Nutritional Biochemistry, 22, 38-45. doi:10.1016/j.jnutbio.2009.11.009
[20] Li, Y., Sugiyama, E., Yokoyama, S., Jiang, L., Tanaka, N. and Aoyama, T. (2008) Molecular mechanism of agespecific hepatic lipid accumulation in PPARalpha (+/-): LDLR (+/-) mice, an obese mouse model. Lipids, 43, 301-312. doi:10.1007/s11745-008-3161-x
[21] Heid, H.W., Schnolzer, M. and Keenan, T.W. (1996) Adipocyte differentiation-related protein is secreted into milk as a constituent of milk lipid globule membrane. Biochemical Journal, 320, 1025-1030.
[22] Bulankina, A.V., Deggerich, A., Wenzel, D., Mutenda, K., Wittmann, J.G., Rudolph, M.G., Burger, K.N.J. and Honing, S. (2009) TIP47 functions in the biogenesis of lipid droplets. The Journal of Cell Biology, 185, 641-655. doi:10.1083/jcb.200812042
[23] Wolins, N.E., Quaynor, B.K., Skinner, J.R., Schoenfish, M.J., Tzekov, A. and Bickel, P.E. (2005) S3-12, Adipophilin, and TIP47 Package Lipid in Adipocytes. The Journal of Biological Chemistry, 280, 19146-19155. doi:10.1074/jbc.M500978200
[24] Coen, P.M., Dube, J.J., Amati, F., Stefanovic-Racic, M., Ferrell, R.E., Toledo, F.G. and Goodpaster, B.H. (2010) Insulin resistance is associated with higher intramyocellular triglycerides in type I but not type II myocytes concomitant with higher ceramide content. Diabetes, 59, 8088. doi:10.2337/db09-0988
[25] Chang, B.H., Li, L., Paul, A., Taniguchi, S., Nannegari, V., Heird, W.C. and Chan, L. (2006) Protection against fatty liver but normal adipogenesis in mice lacking adipose differentiation-related protein. Molecular and Cellular Biology, 26, 1063-1076. doi:10.1128/MCB.26.3.1063-1076.2006
[26] Sztalryd, C., Bell, M., Lu, X., Mertz, P., Hickenbottom, S., Chang, B.H., Chan, L., Kimmel, A.R. and Londos, C. (2006) Functional compensation for adipose differentiation-related protein (ADFP) by Tip47 in an ADFP null embryonic cell line. The Journal of Biological Chemistry, 281, 34341-34348. doi:10.1074/jbc.M602497200
[27] Bosma, M., Minnaard, R., Sparks, L.M., Schaart, G., Losen, M., de Baets, M.H., Duimel, H., Kersten, S., Bickel, P.E., Schrauwen, P. and Hesselink, M.K. (2012) The lipid droplet coat protein perilipin 5 also localizes to muscle mitochondria. Histochemistry and Cell Biology, 137, 205-216. doi:10.1007/s00418-011-0888-x
[28] Wolins, N.E., Brasaemle, D.L. and Bickel, P.E. (2006) A proposed model of fat packaging by exchangeable lipid droplet proteins. FEBS Letters, 580, 5484-5491. doi:10.1016/j.febslet.2006.08.040
[29] Wang, H. and Sztalryd, C. (2011) Oxidative tissue: Perilipin 5 links storage with the furnace. Trends in Endocrinology & Metabolism, 22, 197-203. doi:10.1016/j.tem.2011.03.008
[30] Wolins, N.E., Quaynor, B.K., Skinner, J.R., Tzekov, A., Croce, M.A., Gropler, M.C., Varma, V., Yao-Borengasser, A., Rasouli, N., Kern, P.A., Finck, B.N. and Bickel, P.E. (2006) OXPAT/PAT-1 is a PPAR-induced lipid droplet protein that promotes fatty acid utilization. Diabetes, 55, 3418-3428. doi:10.2337/db06-0399
[31] Svedenhag, J., Lithell, H., Juhlin-Dannfelt, A. and Henriksson, J. (1983) Increase in skeletal muscle lipoprotein lipase following endurance training in man. Atherosclerosis, 49, 203-207. doi:10.1016/0021-9150(83)90198-3
[32] Jaye, M., Lynch, K.J., Krawiec, J., Marchadier, D., Maugeais, C., Doan, K., South, V., Amin, D., Perrone, M. and Rader, D.J. (1999) A novel endothelial-derived lipase that modulates HDL metabolism. Nature Genetics, 21, 424428. doi:10.1038/7766
[33] Choi, S.Y., Hirata, K., Ishida, T., Quertermous, T. and Cooper, A.D. (2002) Endothelial lipase: A new lipase on the block. The Journal of Lipid Research, 43, 1763-1769. doi:10.1194/jlr.R200011-JLR200
[34] Jin, W., Millar, J.S., Broedl, U., Glick, J.M. and Rader, D.J. (2003) Inhibition of endothelial lipase causes increased HDL cholesterol levels in vivo. Journal of Clinical Investigation, 111, 357-362.

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