Abstract
A maternal high fat diet (HFD) can have adverse effects on skeletal muscle development. Skeletal muscle PLIN proteins (PLIN2, 3 and 5) are thought to play critical roles in lipid metabolism, however effects of HFD on PLIN and lipases (HSL, ATGL, CGI-58) in mothers as well as their offspring have yet to be investigated. The primary objective of this study was to determine whether maternal HFD would influence skeletal muscle lipase and PLIN protein content in offspring at weaning (19d) and young adulthood (3mo). Female rats (28d old, n = 9/group) were fed control (CON, AIN93G, 7 % soybean oil) or HFD (AIN93G, 20 % lard) for 10 weeks prior to mating and throughout pregnancy and lactation. All offspring were weaned to CON [n = 18/group, 1 female and 1 male pup per litter were studied at weaning (19d) and 3mo of age]. There was no effect of sex for the main outcomes measured in plantaris, therefore male and female data was combined. Maternal HFD resulted in higher triacylglycerol content in pups at 3mo (p < 0.05), as well as in the dams (p = 0.015). Maternal HFD resulted in higher PLIN5 content in pups at weaning and 3mo (p = 0.05). PLIN2 and PLIN5 content decreased at 3mo versus weaning (p < 0.001). HFD dams had a higher PLIN3 content (p = 0.016). Diet had no effect on ATGL, CGI-58, or HSL content. In conclusion, exposure to a maternal HFD resulted in higher skeletal muscle lipid and PLIN5 content in plantaris of offspring through to young adulthood.
Similar content being viewed by others
Abbreviations
- HFD:
-
High fat diet
- PLIN:
-
Perilipin
- ATGL:
-
Adipose triglyceride lipase
- HSL:
-
Hormone sensitive lipase
- CON:
-
Control diet
- ORO:
-
Oil red O
References
Alsted TJ, Nybo L, Schweiger M, Fledelius C, Jacobsen P, Zimmermann R, Zechner R, Kiens B (2009) Adipose triglyceride lipase in human skeletal muscle is upregulated by exercise training. Am J Physiol Endocrinol Metab 296:E445–E453
Anderson EJ, Lustig ME, Boyle KE, Woodlief TL, Kane DA, Lin CT, Price JW 3rd, Kang L, Rabinovitch PS, Szeto HH, Houmard JA, Cortright RN, Wasserman DH, Neufer PD (2009) Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J Clin Investig 119:573–581
Badin PM, Vila IK, Louche K, Mairal A, Marques MA, Bourlier V, Tavernier G, Langin D, Moro C (2013) High-fat diet-mediated lipotoxicity and insulin resistance is related to impaired lipase expression in mouse skeletal muscle. Endocrinology 154:1444–1453
Bayol SA, Macharia R, Farrington SJ, Simbi BH, Stickland NC (2009) Evidence that a maternal “junk food” diet during pregnancy and lactation can reduce muscle force in offspring. Eur J Nutr 48:62–65
Bayol SA, Simbi BH, Stickland NC (2005) A maternal cafeteria diet during gestation and lactation promotes adiposity and impairs skeletal muscle development and metabolism in rat offspring at weaning. J Physiol 567:951–961
Bonen A, Parolin ML, Steinberg GR, Calles-Escandon J, Tandon NN, Glatz JF, Luiken JJ, Heigenhauser GJ, Dyck DJ (2004) Triacylglycerol accumulation in human obesity and type 2 diabetes is associated with increased rates of skeletal muscle fatty acid transport and increased sarcolemmal FAT/CD36. FASEB J 18:1144–1146
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 (2012) Perilipin 2 improves insulin sensitivity in skeletal muscle despite elevated intramuscular lipid levels. Diabetes 61:2679–2690
Bosma M, Minnaard R, Sparks LM, Schaart G, Losen M, de Baets MH, Duimel H, Kersten S, Bickel PE, Schrauwen P, Hesselink MK (2012) The lipid droplet coat protein perilipin 5 also localizes to muscle mitochondria. Histochem Cell Biol 137:205–216
Bosma M, Sparks LM, Hooiveld GJ, Jorgensen JA, Houten SM, Schrauwen P, Kersten S, Hesselink MK (1831) Overexpression of PLIN5 in skeletal muscle promotes oxidative gene expression and intramyocellular lipid content without compromising insulin sensitivity. Biochim Biophys Acta 844–852:2013
Bradley NS, Heigenhauser GJ, Roy BD, Staples EM, Inglis JG, LeBlanc PJ, Peters SJ (1985) The acute effects of differential dietary fatty acids on human skeletal muscle pyruvate dehydrogenase activity. J Appl Physiol 104(1–9):2008
Brasaemle DL (2007) Thematic review series: adipocyte biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis. J Lipid Res 48:2547–2559
Brasaemle DL, Barber T, Wolins NE, Serrero G, Blanchette-Mackie EJ, Londos C (1997) Adipose differentiation-related protein is an ubiquitously expressed lipid storage droplet-associated protein. J Lipid Res 38:2249–2263
Brown DA (2001) Lipid droplets: proteins floating on a pool of fat. Curr Biol 11:R446–R449
Bulankina AV, Deggerich A, Wenzel D, Mutenda K, Wittmann JG, Rudolph MG, Burger KN, Honing S (2009) TIP47 functions in the biogenesis of lipid droplets. J Cell Biol 185:641–655
Dalen KT, Dahl T, Holter E, Arntsen B, Londos C, Sztalryd C, Nebb HI (2007) LSDP5 is a PAT protein specifically expressed in fatty acid oxidizing tissues. Biochim Biophys Acta 1771:210–227
de Wilde J, Smit E, Snepvangers FJ, de Wit NW, Mohren R, Hulshof MF, Mariman EC (2010) Adipophilin protein expression in muscle–a possible protective role against insulin resistance. FEBS J 277:761–773
Ducharme NA, Bickel PE (2008) Lipid droplets in lipogenesis and lipolysis. Endocrinology 149:942–949
ED O (1993) Guide to the care and use of experimental animals, 2nd ed. In: Canadian Council on Animal Care 1
Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226:497–509
Franco JG, Fernandes TP, Rocha CP, Calvino C, Pazos-Moura CC, Lisboa PC, Moura EG, Trevenzoli IH (2012) Maternal high-fat diet induces obesity and adrenal and thyroid dysfunction in male rat offspring at weaning. J Physiol 590:5503–5518
Fukushima M, Enjoji M, Kohjima M, Sugimoto R, Ohta S, Kotoh K, Kuniyoshi M, Kobayashi K, Imamura M, Inoguchi T, Nakamuta M, Nawata H (2005) Adipose differentiation related protein induces lipid accumulation and lipid droplet formation in hepatic stellate cells. In Vitro Cell Dev Biol Anim 41:321–324
Gao J, Serrero G (1999) Adipose differentiation related protein (ADRP) expressed in transfected COS-7 cells selectively stimulates long chain fatty acid uptake. J Biol Chem 274:16825–16830
Hancock CR, Han DH, Chen M, Terada S, Yasuda T, Wright DC, Holloszy JO (2008) High-fat diets cause insulin resistance despite an increase in muscle mitochondria. Proc Natl Acad Sci USA 105:7815–7820
Hsieh K, Lee YK, Londos C, Raaka BM, Dalen KT, Kimmel AR (2012) Perilipin family members preferentially sequester to either triacylglycerol-specific or cholesteryl-ester-specific intracellular lipid storage droplets. J Cell Sci 125:4067–4076
Imamura M, Inoguchi T, Ikuyama S, Taniguchi S, Kobayashi K, Nakashima N, Nawata H (2002) ADRP stimulates lipid accumulation and lipid droplet formation in murine fibroblasts. Am J Physiol Endocrinol Metab 283:E775–E783
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
Kishimoto K, Urade R, Ogawa T, Moriyama T (2001) Nondestructive quantification of neutral lipids by thin-layer chromatography and laser-fluorescent scanning: suitable methods for “lipidome” analysis. Biochem Biophys Res Commun 281:657–662
Koopman R, Schaart G, Hesselink MK (2001) Optimisation of oil red O staining permits combination with immunofluorescence and automated quantification of lipids. Histochem Cell Biol 116:63–68
Listenberger LL, Ostermeyer-Fay AG, Goldberg EB, Brown WJ, Brown DA (2007) Adipocyte differentiation-related protein reduces the lipid droplet association of adipose triglyceride lipase and slows triacylglycerol turnover. J Lipid Res 48:2751–2761
Liu P, Ying Y, Zhao Y, Mundy DI, Zhu M, Anderson RG (2004) Chinese hamster ovary K2 cell lipid droplets appear to be metabolic organelles involved in membrane traffic. J Biol Chem 279:3787–3792
Londos C, Sztalryd C, Tansey JT, Kimmel AR (2005) Role of PAT proteins in lipid metabolism. Biochimie 87:45–49
Macpherson RE, Herbst EA, Reynolds EJ, Vandenboom R, Roy BD, Peters SJ (2012) Subcellular localization of skeletal muscle lipid droplets and PLIN family proteins OXPAT and ADRP at rest and following contraction in rat soleus muscle. Am J Physiol Regul Integr Comp Physiol 302:R29–R36
Macpherson RE, Ramos S, Vandenboom R, Roy BD, Peters SJ (2013) Skeletal muscle PLIN proteins, ATGL and CGI-58, interactions at rest and following stimulated contraction. Am J Physiol Regul Integr Comp Physiol 304:R644
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
Mahadevappa VG, Holub BJ (1987) Quantitative loss of individual eicosapentaenoyl-relative to arachidonoyl-containing phospholipids in thrombin-stimulated human platelets. J Lipid Res 28:1275–1280
Minnaard R, Schrauwen P, Schaart G, Jorgensen JA, Lenaers E, Mensink M, Hesselink MK (2009) Adipocyte differentiation-related protein and OXPAT in rat and human skeletal muscle: involvement in lipid accumulation and type 2 diabetes mellitus. J Clin Endocrinol Metab 94:4077–4085
Miotto PM, Castelli LM, Amoye F, Leblanc PJ, Peters SJ, Roy BD, Ward WE (2013) Maternal high fat feeding does not have long-lasting effects on body composition and bone health in female and male wistar rat offspring at young adulthood. Molecules 18:15094–15109
Moore HP, Silver RB, Mottillo EP, Bernlohr DA, Granneman JG (2005) Perilipin targets a novel pool of lipid droplets for lipolytic attack by hormone-sensitive lipase. J Biol Chem 280:43109–43120
Moro C, Bajpeyi S, Smith SR (2007) Determinants of intramyocellular triglyceride turnover: implications for insulin sensitivity. Am J Physiol Endocrinol Metab 294:E203–E213
Murphy DJ (2001) The biogenesis and functions of lipid bodies in animals, plants and microorganisms. Prog Lipid Res 40:325–438
Peters SJ, Samjoo IA, Devries MC, Stevic I, Robertshaw HA, Tarnopolsky MA (2012) Perilipin family (PLIN) proteins in human skeletal muscle: the effect of sex, obesity, and endurance training. Appl Physiol Nutr Metab 37:724–735
Prats C, Donsmark M, Qvortrup K, Londos C, Sztalryd C, Holm C, Galbo H, Ploug T (2006) Decrease in intramuscular lipid droplets and translocation of HSL in response to muscle contraction and epinephrine. J Lipid Res 47:2392–2399
Purcell RH, Sun B, Pass LL, Power ML, Moran TH, Tamashiro KL (2011) Maternal stress and high-fat diet effect on maternal behavior, milk composition, and pup ingestive behavior. Physiol Behav 104:474–479
Ramos SV, MacPherson RE, Turnbull PC, Bott KN, LeBlanc P, Ward WE, Peters SJ (2014) Higher PLIN5 but not PLIN3 content in isolated skeletal muscle mitochondria following acute in vivo contraction in rat hindlimb. Physiol Rep 2
Russell AP (2004) Lipotoxicity: the obese and endurance-trained paradox. Int J Obes Relat Metab Disord 28(suppl 4):S66–S71
Schrauwen-Hinderling VB, Kooi ME, Hesselink MK, Moonen-Kornips E, Schaart G, Mustard KJ, Hardie DG, Saris WH, Nicolay K, Schrauwen P (2005) Intramyocellular lipid content and molecular adaptations in response to a 1-week high-fat diet. Obes Res 13:2088–2094
Shankar K, Harrell A, Liu X, Gilchrist JM, Ronis MJ, Badger TM (2008) Maternal obesity at conception programs obesity in the offspring. Am J Physiol Regul Integr Comp Physiol 294:R528–R538
Shaw CS, Shepherd SO, Wagenmakers AJ, Hansen D, Dendale P, van Loon LJ (2012) Prolonged exercise training increases intramuscular lipid content and perilipin 2 expression in type I muscle fibres of patients with type 2 diabetes. Am J Physiol Endocr Metab
Shaw CS, Sherlock M, Stewart PM, Wagenmakers AJ (2009) Adipophilin distribution and colocalization with lipid droplets in skeletal muscle. Histochem Cell Biol 131:575–581
Shepherd SO, Cocks M, Tipton KD, Ranasinghe AM, Barker TA, Burniston JG, Wagenmakers AJ, Shaw CS (2012) Preferential utilization of perilipin 2-associated intramuscular triglycerides during 1 h of moderate-intensity endurance-type exercise. Exp Physiol 97:970–980
Shepherd SO, Cocks M, Tipton KD, Ranasinghe AM, Barker TA, Burniston JG, Wagenmakers AJ, Shaw CS (2013) Sprint interval and traditional endurance training increase net intramuscular triglyceride breakdown and expression of perilipin 2 and 5. J Physiol 591:657–675
Simar D, Chen H, Lambert K, Mercier J, Morris MJ (2012) Interaction between maternal obesity and post-natal over-nutrition on skeletal muscle metabolism. Nutr Metab Cardiovasc Dis 22:269–276
Stellingwerff T, Boon H, Jonkers RA, Senden JM, Spriet LL, Koopman R, van Loon LJ (2007) Significant intramyocellular lipid use during prolonged cycling in endurance-trained males as assessed by three different methodologies. Am J Physiol Endocr Metab 292:E1715–E1723
Sun B, Purcell RH, Terrillion CE, Yan J, Moran TH, Tamashiro KL (2012) Maternal high-fat diet during gestation or suckling differentially affects offspring leptin sensitivity and obesity. Diabetes 61:2833–2841
Tansey JT, Sztalryd C, Hlavin EM, Kimmel AR, Londos C (2004) The central role of perilipin a in lipid metabolism and adipocyte lipolysis. IUBMB Life 56:379–385
Timmers S, de Vogel-van den Bosch J, Hesselink MK, van Beurden D, Schaart G, Ferraz MJ, Losen M, Martinez-Martinez P, De Baets MH, Aerts JM, Schrauwen P (2011) Paradoxical increase in TAG and DAG content parallel the insulin sensitizing effect of unilateral DGAT1 overexpression in rat skeletal muscle. PloS One 6:e14503
Unger RH, Scherer PE (2010) Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity. Trends Endocr Metab 21:345–352
van Loon LJ, Koopman R, Manders R, van der Weegen W, van Kranenburg GP, Keizer HA (2004) Intramyocellular lipid content in type 2 diabetes patients compared with overweight sedentary men and highly trained endurance athletes. Am J Physiol Endocr Metab 287:E558–E565
van Loon LJ, Koopman R, Stegen JH, Wagenmakers AJ, Keizer HA, Saris WH (2003) Intramyocellular lipids form an important substrate source during moderate intensity exercise in endurance-trained males in a fasted state. J Physiol 553:611–625
Virtue S, Vidal-Puig A (1801) Adipose tissue expandability, lipotoxicity and the metabolic syndrome—an allostatic perspective. Biochim Biophys Acta 338–349:2010
Wainwright PE (1998) Issues of design and analysis relating to the use of multiparous species in developmental nutritional studies. J Nutr 128:661–663
Wang H, Sreenevasan U, Hu H, Saladino A, Polster BM, Lund LM, Gong DW, Stanley WC, Sztalryd C (2011) Perilipin 5, a lipid droplet-associated protein, provides physical and metabolic linkage to mitochondria. J Lipid Res 52:2159–2168
White CL, Purpera MN, Morrison CD (2009) Maternal obesity is necessary for programming effect of high-fat diet on offspring. Am J Physiol Regul Integr Comp Physiol 296:R1464–R1472
Wolins NE, Quaynor BK, Skinner JR, Schoenfish MJ, Tzekov A, Bickel PE (2005) S3-12, Adipophilin, and TIP47 package lipid in adipocytes. J Biol Chem 280:19146–19155
Wolins NE, Quaynor BK, Skinner JR, Tzekov A, Croce MA, Gropler MC, Varma V, Yao-Borengasser A, Rasouli N, Kern PA, Finck BN, Bickel PE (2006) OXPAT/PAT-1 is a PPAR-induced lipid droplet protein that promotes fatty acid utilization. Diabetes 55:3418–3428
Wolins NE, Rubin B, Brasaemle DL (2001) TIP47 associates with lipid droplets. J Biol Chem 276:5101–5108
Acknowledgments
The in vivo portion of this study was funded through start-up funding from Brock University to W. Ward. Analyses were funded by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grant to S. J. Peters. Lipid analyses were funded by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant to P.J. LeBlanc. Laboratory infrastructure support was provided by the Canadian Foundation for Innovation (B. Roy), the Ontario Innovation Trust (B. Roy), and NSERC. R. MacPherson is the recipient of an Ontario Graduate Scholarship in Science and Technology, as well as a NSERC Doctoral Postgraduate Scholarship. L. Castelli received graduate student support through an Ontario Graduate Scholarship (OGS). P. Miotto received graduate student support through a Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best Canada Graduate Scholarship. W. Ward holds a Canada Research Chair in Bone and Muscle Development.
Conflict of interest
No conflicts of interest, financial or otherwise, are declared by the authors.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
MacPherson, R.E.K., Castelli, L.M., Miotto, P.M. et al. A Maternal High Fat Diet Has Long-Lasting Effects on Skeletal Muscle Lipid and PLIN Protein Content in Rat Offspring at Young Adulthood. Lipids 50, 205–217 (2015). https://doi.org/10.1007/s11745-014-3985-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11745-014-3985-5