A 7-day high-fat, high-calorie diet induces fibre-specific increases in intramuscular triglyceride and perilipin protein expression in human skeletal muscle

K L Whytock, S A Parry, M C Turner, R M Woods, L J James, R A Ferguson, M Ståhlman, J Borén, J A Strauss, M Cocks, A J M Wagenmakers, C J Hulston, S O Shepherd, K L Whytock, S A Parry, M C Turner, R M Woods, L J James, R A Ferguson, M Ståhlman, J Borén, J A Strauss, M Cocks, A J M Wagenmakers, C J Hulston, S O Shepherd

Abstract

Key points: We have recently shown that a high-fat, high-calorie (HFHC) diet decreases whole body glucose clearance without impairing skeletal muscle insulin signalling, in healthy lean individuals. These diets are also known to increase skeletal muscle IMTG stores, but the effect on lipid metabolites leading to skeletal muscle insulin resistance has not been investigated. This study measured the effect of 7 days' HFHC diet on (1) skeletal muscle concentration of lipid metabolites, and (2) potential changes in the perilipin (PLIN) content of the lipid droplets storing intramuscular triglyceride (IMTG). The HFHC diet increased PLIN3 protein expression and redistributed PLIN2 to lipid droplet stores in type I fibres. The HFHC diet increased IMTG content in type I fibres, while lipid metabolite concentrations remained the same. The data suggest that the increases in IMTG stores assists in reducing the accumulation of lipid metabolites known to contribute to skeletal muscle insulin resistance.

Abstract: A high-fat, high-calorie (HFHC) diet reduces whole body glucose clearance without impairing skeletal muscle insulin signalling in healthy lean individuals. HFHC diets also increase skeletal muscle lipid stores. However, unlike certain lipid metabolites, intramuscular triglyceride (IMTG) stored within lipid droplets (LDs) does not directly contribute to skeletal muscle insulin resistance. Increased expression of perilipin (PLIN) proteins and colocalisation to LDs has been shown to assist in IMTG storage. We aimed to test the hypothesis that 7 days on a HFHC diet increases IMTG content while minimising accumulation of lipid metabolites known to disrupt skeletal muscle insulin signalling in sedentary and obese individuals. We also aimed to identify changes in expression and subcellular distribution of proteins involved in IMTG storage. Muscle biopsies were obtained from the m. vastus lateralis of 13 (11 males, 2 females) healthy lean individuals (age: 23 ± 2.5 years; body mass index: 24.5 ± 2.4 kg m-2 ), following an overnight fast, before and after consuming a high-fat (64% energy), high-calorie (+47% kcal) diet for 7 days. After the HFHC diet, IMTG content increased in type I fibres only (+101%; P < 0.001), whereas there was no change in the concentration of either total diacylglycerol (P = 0.123) or total ceramides (P = 0.150). Of the PLINs investigated, only PLIN3 content increased (+50%; P < 0.01) solely in type I fibres. LDs labelled with PLIN2 increased (+80%; P < 0.01), also in type I fibres only. We propose that these adaptations of LDs support IMTG storage and minimise accumulation of lipid metabolites to protect skeletal muscle insulin signalling following 7 days' HFHC diet.

Keywords: confocal immunohistochemistry; high fat; intramuscular triglyceride; perilipin.

© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.

References

    1. Amati F, Dube JJ, Alvarez-Carnero E, Edreira MM, Chomentowski P, Coen PM, Switzer GE, Bickel PE, Stefanovic-Racic M, Toledo FG & Goodpaster BH (2011). Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: Another paradox in endurance-trained athletes? Diabetes 60, 2588-2597.
    1. Amrutkar M, Cansby E, Nunez-Duran E, Pirazzi C, Stahlman M, Stenfeldt E, Smith U, Boren J & Mahlapuu M (2015). Protein kinase STK25 regulates hepatic lipid partitioning and progression of liver steatosis and NASH. FASEB J 29, 1564-1576.
    1. Bakker LE, van Schinkel LD, Guigas B, Streefland TC, Jonker JT, van Klinken JB, van der Zon GC, Lamb HJ, Smit JW, Pijl H, Meinders AE & Jazet IM (2014). A 5-day high-fat, high-calorie diet impairs insulin sensitivity in healthy, young South Asian men but not in Caucasian men. Diabetes 63, 248-258.
    1. Bergstrӧm J (1975). Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Invest 35, 609-616.
    1. Bersuker K & Olzmann JA (2017). Establishing the lipid droplet proteome: Mechanisms of lipid droplet protein targeting and degradation. Biochim Biophys Acta Mol Cell Biol Lipids 1862, 1166-1177.
    1. Boden G, Chen X, Ruiz J, White JV & Rossetti L (1994). Mechanisms of fatty acid-induced inhibition of glucose uptake. J Clin Invest 93, 2438-2446.
    1. 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.
    1. 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.
    1. Chee C, Shannon CE, Burns A, Selby AL, Wilkinson D, Smith K, Greenhaff PL & Stephens FB (2016). Relative contribution of intramyocellular lipid to whole-body fat oxidation is reduced with age but subsarcolemmal lipid accumulation and insulin resistance are only associated with overweight individuals. Diabetes 65, 840-850.
    1. Chow LS, Mashek DG, Austin E, Eberly LE, Persson XM, Mashek MT, Seaquist ER & Jensen MD (2014). Training status diverges muscle diacylglycerol accumulation during free fatty acid elevation. Am J Physiol Endocrinol Metab 307, E124-E131.
    1. Covington JD, Noland RC, Hebert RC, Masinter BS, Smith SR, Rustan AC, Ravussin E & Bajpeyi S (2015). Perilipin 3 differentially regulates skeletal muscle lipid oxidation in active, sedentary, and type 2 diabetic males. J Clin Endocrinol Metab 100, 3683-3692.
    1. 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.
    1. Daemen S, Gemmink A, Brouwers B, Meex RCR, Huntjens PR, Schaart G, Moonen-Kornips E, Jorgensen J, Hoeks J, Schrauwen P & Hesselink MKC (2018). Distinct lipid droplet characteristics and distribution unmask the apparent contradiction of the athlete's paradox. Mol Metab 17, 71-81.
    1. DeFronzo RA & Tripathy D (2009). Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care 32(Suppl 2), S157-S163.
    1. Ferrannini E, Smith JD, Cobelli C, Toffolo G, Pilo A & DeFronzo RA (1985). Effect of insulin on the distribution and disposition of glucose in man. J Clin Invest 76, 357-364.
    1. Garcia-Roves P, Huss JM, Han DH, Hancock CR, Iglesias-Gutierrez E, Chen M & Holloszy JO (2007). Raising plasma fatty acid concentration induces increased biogenesis of mitochondria in skeletal muscle. Proc Natl Acad Sci U S A 104, 10709-10713.
    1. Gemmink A, Bakker LE, Guigas B, Kornips E, Schaart G, Meinders AE, Jazet IM & Hesselink MK (2017). Lipid droplet dynamics and insulin sensitivity upon a 5-day high-fat diet in Caucasians and South Asians. Sci Rep 7, 42393.
    1. Gemmink A, Bosma M, Kuijpers HJ, Hoeks J, Schaart G, van Zandvoort MA, Schrauwen P & Hesselink MK (2016). Decoration of intramyocellular lipid droplets with PLIN5 modulates fasting-induced insulin resistance and lipotoxicity in humans. Diabetologia 59, 1040-1048.
    1. Gemmink A, Daemen S, Brouwers B, Huntjens PR, Schaart G, Moonen-Kornips E, Jorgensen J, Hoeks J, Schrauwen P & Hesselink MKC (2018). Dissociation of intramyocellular lipid storage and insulin resistance in trained athletes and type 2 diabetes patients; involvement of perilipin 5? J Physiol 596, 857-868.
    1. 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, 5755-5761.
    1. Guo Z (2001). Triglyceride content in skeletal muscle: Variability and the source. Anal Biochem 296, 1-8.
    1. 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 U S A 105, 7815-7820.
    1. Harris LA, Shew TM, Skinner JR & Wolins NE (2012). A single centrifugation method for isolating fat droplets from cells and tissues. J Lipid Res 53, 1021-1025.
    1. Hesselink MKC, Daemen S, van Polanen N & Gemmink A (2017). What are the benefits of being big? J Physiol 595, 5409-5410.
    1. Hoppeler H, Billeter R, Horvath PJ, Leddy JJ & Pendergast DR (1999). Muscle structure with low- and high-fat diets in well-trained male runners. Int J Sports Med 20, 522-526.
    1. Hulston CJ, Churnside AA & Venables MC (2015). Probiotic supplementation prevents high-fat, overfeeding-induced insulin resistance in human subjects. Br J Nutr 113, 596-602.
    1. 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.
    1. Itani SI, Ruderman NB, Schmieder F & Boden G (2002). Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IκB-α. Diabetes 51, 2005-2011.
    1. Jain SS, Paglialunga S, Vigna C, Ludzki A, Herbst EA, Lally JS, Schrauwen P, Hoeks J, Tupling AR, Bonen A & Holloway GP (2014). High-fat diet-induced mitochondrial biogenesis is regulated by mitochondrial-derived reactive oxygen species activation of CaMKII. Diabetes 63, 1907-1913.
    1. Katz LD, Glickman MG, Rapoport S, Ferrannini E & DeFronzo RA (1983). Splanchnic and peripheral disposal of oral glucose in man. Diabetes 32, 675-679.
    1. Kelley DE, Goodpaster B, Wing RR & Simoneau JA (1999). Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Am J Physiol 277, E1130-E1141.
    1. Kleinert M, Parker BL, Chaudhuri R, Fazakerley DJ, Serup A, Thomas KC, Krycer JR, Sylow L, Fritzen AM, Hoffman NJ, Jeppesen J, Schjerling P, Ruegg MA, Kiens B, James DE & Richter EA (2016). mTORC2 and AMPK differentially regulate muscle triglyceride content via Perilipin 3. Mol Metab 5, 646-655.
    1. Koves TR, Sparks LM, Kovalik JP, Mosedale M, Arumugam R, DeBalsi KL, Everingham K, Thorne L, Phielix E, Meex RC, Kien CL, Hesselink MK, Schrauwen P & Muoio DM (2013). PPARγ coactivator-1α contributes to exercise-induced regulation of intramuscular lipid droplet programming in mice and humans. J Lipid Res 54, 522-534.
    1. Krahmer N, Guo Y, Wilfling F, Hilger M, Lingrell S, Heger K, Newman HW, Schmidt-Supprian M, Vance DE, Mann M, Farese RV Jr & Walther TC (2011). Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP:phosphocholine cytidylyltransferase. Cell Metab 14, 504-515.
    1. Kuramoto K, Okamura T, Yamaguchi T, Nakamura TY, Wakabayashi S, Morinaga H, Nomura M, Yanase T, Otsu K, Usuda N, Matsumura S, Inoue K, Fushiki T, Kojima Y, Hashimoto T, Sakai F, Hirose F & Osumi T (2012). Perilipin 5, a lipid droplet-binding protein, protects heart from oxidative burden by sequestering fatty acid from excessive oxidation. J Biol Chem 287, 23852-23863.
    1. Laurens C, Bourlier V, Mairal A, Louche K, Badin PM, Mouisel E, Montagner A, Marette A, Tremblay A, Weisnagel JS, Guillou H, Langin D, Joanisse DR & Moro C (2016). Perilipin 5 fine-tunes lipid oxidation to metabolic demand and protects against lipotoxicity in skeletal muscle. Sci Rep 6, 38310.
    1. Lofgren L, Forsberg GB & Stahlman M (2016). The BUME method: A new rapid and simple chloroform-free method for total lipid extraction of animal tissue. Sci Rep 6, 27688.
    1. Louche K, Badin PM, Montastier E, Laurens C, Bourlier V, de Glisezinski I, Thalamas C, Viguerie N, Langin D & Moro C (2013). Endurance exercise training up-regulates lipolytic proteins and reduces triglyceride content in skeletal muscle of obese subjects. J Clin Endocrinol Metab 98, 4863-4871.
    1. Lundsgaard AM, Sjoberg KA, Hoeg LD, Jeppesen J, Jordy AB, Serup AK, Fritzen AM, Pilegaard H, Myrmel LS, Madsen L, Wojtaszewski JFP, Richter EA & Kiens B (2017). Opposite regulation of insulin sensitivity by dietary lipid versus carbohydrate excess. Diabetes 66, 2583-2595.
    1. Mifflin MD, St Jeor ST, Hill LA, Scott BJ, Daugherty SA & Koh YO (1990). A new predictive equation for resting energy expenditure in healthy individuals. Am J Clin Nutr 51, 241-247.
    1. Murphy RC, James PF, McAnoy AM, Krank J, Duchoslav E & Barkley RM (2007). Detection of the abundance of diacylglycerol and triacylglycerol molecular species in cells using neutral loss mass spectrometry. Anal Biochem 366, 59-70.
    1. Nielsen J, Christensen AE, Nellemann B & Christensen B (2017). Lipid droplet size and location in human skeletal muscle fibers are associated with insulin sensitivity. Am J Physiol Endocrinol Metab 313, E721-E730.
    1. Parry SA, Smith JR, Corbett TRB, Woods RM & Hulston CJ (2017). Short-term, high-fat overfeeding impairs glycaemic control but does not alter gut hormone responses to a mixed meal tolerance test in healthy, normal-weight individuals. Br J Nutr 117, 48-55.
    1. Parry SA, Turner MC, Woods RM, James LJ, Ferguson RA, Cocks M, Whytock KL, Strauss JA, Shepherd SO, Wagenmakers AJM, van Hall G & Hulston CJ (2020). High-fat overfeeding impairs peripheral glucose metabolism and muscle microvascular eNOS Ser1177 phosphorylation. J Clin Endocrinol Metab 105, dgz018.
    1. 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, e12154.
    1. Robenek H, Hofnagel O, Buers I, Robenek MJ, Troyer D & Severs NJ (2006). Adipophilin-enriched domains in the ER membrane are sites of lipid droplet biogenesis. J Cell Sci 119, 4215-4224.
    1. Shaw CS, Jones DA & Wagenmakers AJ (2008). Network distribution of mitochondria and lipid droplets in human muscle fibres. Histochem Cell Biol 129, 65-72.
    1. Shaw CS, Shepherd SO, Wagenmakers AJM, Hansen D, Dendale P & van Loon LJC (2012). Prolonged exercise training increases intramuscular lipid content and perilipin 2 expression in type I muscle fibers of patients with type 2 diabetes. Am J Physiol Endocrinol Metab 303, E1158-E1165.
    1. 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.
    1. 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.
    1. Shepherd SO, Cocks M, Tipton KD, Witard OC, Ranasinghe AM, Barker TA, Wagenmakers AJ & Shaw CS (2014). Resistance training increases skeletal muscle oxidative capacity and net intramuscular triglyceride breakdown in type I and II fibres of sedentary males. Exp Physiol 99, 894-908.
    1. Shepherd SO, Strauss JA, Wang Q, Dube JJ, Goodpaster B, Mashek DG & Chow LS (2017). Training alters the distribution of perilipin proteins in muscle following acute free fatty acid exposure. J Physiol 595, 5587-5601.
    1. Staron RS, Hagerman FC, Hikida RS, Murray TF, Hostler DP, Crill MT, Ragg KE & Toma K (2000). Fiber type composition of the vastus lateralis muscle of young men and women. J Histochem Cytochem 48, 623-629.
    1. Stratford S, Hoehn KL, Liu F & Summers SA (2004). Regulation of insulin action by ceramide: Dual mechanisms linking ceramide accumulation to the inhibition of Akt/protein kinase B. J Biol Chem 279, 36608-36615.
    1. Strauss JA, Shaw CS, Bradley H, Wilson OJ, Dorval T, Pilling J & Wagenmakers AJ (2016). Immunofluorescence microscopy of SNAP23 in human skeletal muscle reveals colocalization with plasma membrane, lipid droplets, and mitochondria. Physiol Rep 4, e12662.
    1. Szendroedi J, Yoshimura T, Phielix E, Koliaki C, Marcucci M, Zhang D, Jelenik T, Muller J, Herder C, Nowotny P, Shulman GI & Roden M (2014). Role of diacylglycerol activation of PKCθ in lipid-induced muscle insulin resistance in humans. Proc Natl Acad Sci U S A 111, 9597-9602.
    1. 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 Endocrinol Metab 287, E558-E565.
    1. Watt MJ & Cheng Y (2017). Triglyceride metabolism in exercising muscle. Biochim Biophys Acta 1862, 1250-1259.
    1. Whytock KL, Shepherd SO, Wagenmakers AJM & Strauss JA (2018). Hormone-sensitive lipase preferentially redistributes to lipid droplets associated with perilipin-5 in human skeletal muscle during moderate-intensity exercise. J Physiol 596, 2077-2090.
    1. 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.
    1. Wolins NE, Rubin B & Brasaemle DL (2001). TIP47 associates with lipid droplets. J Biol Chem 276, 5101-5108.
    1. Yu C, Chen Y, Cline GW, Zhang D, Zong H, Wang Y, Bergeron R, Kim JK, Cushman SW, Cooney GJ, Atcheson B, White MF, Kraegen EW & Shulman GI (2002). Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem 277, 50230-50236.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever