Endurance Training Modulates Intramyocellular Lipid Compartmentalization and Morphology in Skeletal Muscle of Lean and Obese Women
Abstract
CONTEXT: The accumulation of intramyocellular lipids (IMCLs) and mitochondrial dysfunction in skeletal muscle have been associated with insulin resistance in obesity. Endurance training (ET) increases mitochondrial content/activity and IMCL content in young, active men and women. We have previously shown that ET alters the size, number, and physical juxtaposition of IMCLs and mitochondria. OBJECTIVE: The purpose of this study was to determine the effects of obesity and ET on mitochondrial function, IMCL content, and IMCL-mitochondria juxtaposition in sedentary lean and obese women. DESIGN, SETTING, SUBJECTS, INTERVENTION, AND MAIN OUTCOME MEASURES: Obese (n = 11) and lean (n = 12), sedentary women were recruited using local advertisements and underwent 12 weeks of ET in our training facility at McMaster University. Blood and muscle biopsy samples (vastus lateralis) were collected before and after ET to measure IMCL and mitochondrial ultrastructure, mitochondrial oxidative capacity, lipid oxidation capacity, and lipid metabolism by-products. RESULTS: Obese women were insulin resistant (homeostasis model assessment of insulin resistance) compared with lean women. ET did not change body weight but increased mitochondrial oxidative and β-oxidation capacity in both groups. ET mediated reorganization of the muscle architecture, whereby IMCL content in the subsarcolemmal region was reduced with a concomitant increase in intermyofibrillar IMCLs. ET increased the percentage of IMCLs in direct contact with mitochondria and did not alter diacylglycerol and ceramide content in either group. CONCLUSIONS: ET mediated positive changes in mitochondrial function and lipid oxidation and induced intracellular IMCL reorganization, which is reflective of greater IMCL turnover capacity in both lean and obese women.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cause-and-effect sequence of intramyocellular lipid accumulation and mitochondrial function remains equivocal, and the two factors are likely linked in a vicious cycle.
“the cause and effect sequence of IMCL accumulation and mitochondrial function remains equivocal and the two factors are likely linked in a “vicious cycle [94]. ””
From Targeting Intramyocellular Lipids to Improve Aging Muscle Function (2025) · cites this paper as [94]
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes
Kelley, D. E., He, J., Menshikova, E. V., & Ritov, V. B. (2002) · Diabetes · doi:10.2337/diabetes.51.10.2944 · Cited by 2,321 · see citing works
Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes
Petersen, K. F., Dufour, S., Befroy, D., Garcia, R., & Shulman, G. I. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031314 · Cited by 2,193 · see citing works
Yu, C., Chen, Y., Cline, G. W., Zhang, D., Zong, H., Wang, Y., Bergeron, R., Kim, J. K., Cushman, S. W., Cooney, G. J., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200958200 · Cited by 1,561 · see citing works
Goodpaster, B. H. (2001) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.86.12.5755 · Cited by 1,194 · see citing works
Table of nonprotein respiratory quotient: an update.
Péronnet, F., & Massicotte, D. (1991) · PubMed · Cited by 1,177 · see citing works
Kelley, D. E., Goodpaster, B., Wing, R. R., & Simoneau, J.-A. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.277.6.e1130 · Cited by 1,096 · see citing works
Lee, C. D., Blair, S. N., & Jackson, A. S. (1999) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/69.3.373 · Cited by 1,027 · see citing works
Goodpaster, B. H., Leland Thaete, F., Simoneau, J.-A., & Kelley, D. E. (1997) · Diabetes · doi:10.2337/diacare.46.10.1579 · Cited by 1,012 · see citing works
Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes
Ritov, V. B., Menshikova, E. V., He, J., Ferrell, R. E., Goodpaster, B. H., & Kelley, D. E. (2005) · Diabetes · doi:10.2337/diabetes.54.1.8 · Cited by 887 · see citing works
Liver and kidney metabolism during prolonged starvation
Owen, O. E., Felig, P., Morgan, A. P., Wahren, J., & Cahill, G. F. (1969) · Journal of Clinical Investigation · doi:10.1172/jci106016 · Cited by 857 · see citing works
Substrate Turnover during Prolonged Exercise in Man
Ahlborg, G., Felig, P., Hagenfeldt, L., Hendler, R., & Wahren, J. (1974) · Journal of Clinical Investigation · doi:10.1172/jci107645 · Cited by 786 · see citing works
Intramuscular lipid content is increased in obesity and decreased by weight loss
Goodpaster, B. H., Theriault, R., Watkins, S. C., & Kelley, D. E. (2000) · Metabolism · doi:10.1016/s0026-0495(00)80010-4 · Cited by 526 · see citing works
Summers, S. A., Garza, L. A., Zhou, H., & Birnbaum, M. J. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.9.5457 · Cited by 475 · see citing works
Obesity as Compared With Physical Activity in Predicting Risk of Coronary Heart Disease in Women
Li, T. Y., Rana, J. S., Manson, J. E., Willett, W. C., Stampfer, M. J., Colditz, G. A., Rexrode, K. M., & Hu, F. B. (2006) · Circulation · doi:10.1161/circulationaha.105.574087 · Cited by 472 · see citing works
Emoto, M., Nishizawa, Y., Maekawa, K., Hiura, Y., Kanda, H., Kawagishi, T., Shoji, T., Okuno, Y., & Morii, H. (1999) · Diabetes Care · doi:10.2337/diacare.22.5.818 · Cited by 457 · see citing works
Tarnopolsky, M. A., Rennie, C. D., Robertshaw, H. A., Fedak-Tarnopolsky, S. N., Devries, M. C., & Hamadeh, M. J. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00472.2006 · Cited by 457 · see citing works
Self-citationRelationship of Physical Activity vs Body Mass Index With Type 2 Diabetes in Women
Weinstein, A. R. (2004) · JAMA · doi:10.1001/jama.292.10.1188 · Cited by 420 · see citing works
Wessel, T. R. (2004) · JAMA · doi:10.1001/jama.292.10.1179 · Cited by 367 · see citing works
Skeletal muscle lipid metabolism with obesity
Hulver, M. W., Berggren, J. R., Cortright, R. N., Dudek, R. W., Thompson, R. P., Pories, W. J., MacDonald, K. G., Cline, G. W., Shulman, G. I., Dohm, G. L., et al. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00514.2002 · Cited by 339 · see citing works
Hu, G., Tuomilehto, J., Silventoinen, K., Barengo, N., & Jousilahti, P. (2004) · European Heart Journal · doi:10.1016/j.ehj.2004.10.020 · Cited by 338 · see citing works
Substrate utilization during endurance exercise in men and women after endurance training
Carter, S. L., Rennie, C., & Tarnopolsky, M. A. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.6.e898 · Cited by 329 · see citing works
Self-citationBruce, C. R., Thrush, A. B., Mertz, V. A., Bezaire, V., Chabowski, A., Heigenhauser, G. J. F., & Dyck, D. J. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00587.2005 · Cited by 328 · see citing works
Lee, J. S., Pinnamaneni, S. K., Eo, S. J., Cho, I. H., Pyo, J. H., Kim, C. K., Sinclair, A. J., Febbraio, M. A., & Watt, M. J. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01438.2005 · Cited by 325 · see citing works
Self-citationHu, G., Tuomilehto, J., Silventoinen, K., Barengo, N. C., Peltonen, M., & Jousilahti, P. (2005) · International Journal of Obesity · doi:10.1038/sj.ijo.0802870 · Cited by 294 · see citing works
Storlien, L., Oakes, N. D., & Kelley, D. E. (2004) · Proceedings of the Nutrition Society · doi:10.1079/pns2004349 · Cited by 291 · see citing works
Effects of training duration on substrate turnover and oxidation during exercise
Phillips, S. M., Green, H. J., Tarnopolsky, M. A., Heigenhauser, G. J. F., Hill, R. E., & Grant, S. (1996) · Journal of Applied Physiology · doi:10.1152/jappl.1996.81.5.2182 · Cited by 279 · see citing works
Self-citationCNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK
Watt, M. J., Dzamko, N. L., Thomas, W. G., Rose‐John, S., Ernst, M., Carling, D., Kemp, B. E., Febbraio, M. A., & Steinberg, G. R. (2006) · Nature Medicine · doi:10.1038/nm1383 · Cited by 275 · see citing works
Self-citationvan Loon, L. J. C., Koopman, R., Manders, R., van der Weegen, W., van Kranenburg, G. P., & Keizer, H. A. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00464.2003 · Cited by 239 · see citing works
Changes in skeletal muscle in males and females following endurance training
Carter, S., Rennie, C. D., Hamilton, S. J., & Tarnopolsky, M. A. (2001) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y01-008 · Cited by 234 · see citing works
Self-citationExercise training increases intramyocellular lipid and oxidative capacity in older adults
Pruchnic, R., Katsiaras, A., He, J., Kelley, D. E., Winters, C., & Goodpaster, B. H. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00459.2003 · Cited by 177 · see citing works
Effects of Obesity on Substrate Utilization during Exercise
Goodpaster, B. H., Wolfe, R. R., & Kelley, D. E. (2002) · Obesity Research · doi:10.1038/oby.2002.78 · Cited by 169 · see citing works
Effects of Weight Loss and Physical Activity on Muscle Lipid Content and Droplet Size
He, J., Goodpaster, B. H., & Kelley, D. E. (2004) · Obesity Research · doi:10.1038/oby.2004.92 · Cited by 152 · see citing works
Key Role for Ceramides in Mediating Insulin Resistance in Human Muscle Cells
Pickersgill, L., Litherland, G. J., Greenberg, A. S., Walker, M., & Yeaman, S. J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611157200 · Cited by 146 · see citing works
Impaired plasma fatty acid oxidation in extremely obese women
Thyfault, J. P., Kraus, R. M., Hickner, R. C., Howell, A. W., Wolfe, R. R., & Dohm, G. L. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00177.2004 · Cited by 122 · see citing works
Physical Activity, Obesity Status, and Glycemic Control
Kavouras, S. A., Panagiotakos, D. B., Pitsavos, C. E., Chrysohoou, C. A., Anastasiou, C. A., Lentzas, Y., & Stefanadis, C. (2007) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e31803084eb · Cited by 90 · see citing works
Devries, M. C., Lowther, S. A., Glover, A. W., Hamadeh, M. J., & Tarnopolsky, M. A. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00510.2007 · Cited by 87 · see citing works
Self-citationOxidation of nonplasma fatty acids during exercise is increased in women with abdominal obesity
Horowitz, J. F., & Klein, S. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.89.6.2276 · Cited by 85 · see citing works
Interrelationships between muscle fibre type, substrate oxidation and body fat
Helge, J. W., Fraser, A., Kriketos, A. D., Jenkins, A. B., Calvert, G. D., Ayre, K. J., & Storlien, L. (1999) · International Journal of Obesity · doi:10.1038/sj.ijo.0801030 · Cited by 79 · see citing works
Increments in skeletal muscle GLUT-1 and GLUT-4 after endurance training in humans
Phillips, S. M., Han, X. X., Green, H. J., & Bonen, A. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.270.3.e456 · Cited by 78 · see citing works
Stevens, J., Evenson, K. R., Thomas, O., Cai, J., & Thomas, R. J. (2004) · International Journal of Obesity · doi:10.1038/sj.ijo.0802770 · Cited by 71 · see citing works
Phillips, S. M., Stewart, B. G., Mahoney, D. J., Hicks, A. L., McCartney, N., Tang, J. E., Wilkinson, S. B., Armstrong, D., & Tarnopolsky, M. A. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00167.2004 · Cited by 71 · see citing works
Self-citationExercise-Induced Alterations in Muscle Lipid Metabolism Improve Insulin Sensitivity
Horowitz, J. F. (2007) · Exercise and Sport Sciences Reviews · doi:10.1097/jes.0b013e318156e084 · Cited by 64 · see citing works
Ezell, D. M., Geiselman, P. J., Anderson, A., Dowdy, M. L., Womble, L. G., Greenway, F., & Zachwieja, J. J. (1999) · International Journal of Obesity · doi:10.1038/sj.ijo.0801037 · Cited by 36 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The potential of endurance exercise-derived exosomes to treat metabolic diseases
Safdar, A., Saleem, A., & Tarnopolsky, M. A. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.76 · Cited by 463 · see citing works
Self-citationLoh, R., Stamatakis, E., Folkerts, D., Allgrove, J. E., & Moir, H. J. (2020) · Sports Medicine · doi:10.1007/s40279-019-01183-w · Cited by 326 · see citing works
Exosomes as Mediators of the Systemic Adaptations to Endurance Exercise
Safdar, A., & Tarnopolsky, M. A. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029827 · Cited by 203 · see citing works
Self-citationPerreault, L., Newsom, S. A., Strauss, A., Kerege, A., Kahn, D. E., Harrison, K. A., Snell-Bergeon, J. K., Nemkov, T., D’Alessandro, A., Jackman, M. R., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.96805 · Cited by 184 · see citing works
Tuning fatty acid oxidation in skeletal muscle with dietary fat and exercise
Fritzen, A. M., Lundsgaard, A.-M., & Kiens, B. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0405-1 · Cited by 180 · see citing works
DiMenna, F. J., & Arad, A. D. (2018) · BMC Sports Science, Medicine and Rehabilitation · doi:10.1186/s13102-018-0110-8 · Cited by 68 · see citing works
Intramyocellular lipid droplets and insulin sensitivity, the human perspective
Gemmink, A., Goodpaster, B. H., Schrauwen, P., & Hesselink, M. K. C. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2017.07.010 · Cited by 62 · see citing works
The lifecycle of skeletal muscle mitochondria in obesity
Pileggi, C. A., Parmar, G., & Harper, M. (2021) · Obesity Reviews · doi:10.1111/obr.13164 · Cited by 61 · see citing works
Factors Influencing Substrate Oxidation During Submaximal Cycling: A Modelling Analysis
Rothschild, J. A., Kilding, A. E., Stewart, T., & Plews, D. J. (2022) · Sports Medicine · doi:10.1007/s40279-022-01727-7 · Cited by 46 · see citing works
McKenzie, A. I., Briggs, R. A., Barrows, K. M., Nelson, D. S., Kwon, O. S., Hopkins, P. N., Higgins, T. F., Marcus, R. L., & Drummond, M. J. (2017) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00714.2016 · Cited by 23 · see citing works
Bosma, M. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.03.007 · Cited by 23 · see citing works
Expanding the Clinical Spectrum of LONP1-Related Mitochondrial Cytopathy
Hannah-Shmouni, F., MacNeil, L., Brady, L., Nilsson, M. I., & Tarnopolsky, M. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00981 · Cited by 19 · see citing works
Self-citationTargeting Intramyocellular Lipids to Improve Aging Muscle Function
Russ, D. W., Manickam, R., & Tipparaju, S. M. (2025) · Lipids in Health and Disease · doi:10.1186/s12944-025-02622-6 · Cited by 15 · see citing works
“As normal mitochondrial function is essential to metabolic flexibility [93], the cause and effect sequence of IMCL accumulation and mitochondrial function remains equivocal and the two factors are likely linked in a “vicious cycle [94].”
Black, M. N., Wilkinson, J. A., Webb, E. K., Kamal, M., Bahniwal, R., McGlory, C., Phillips, S. M., & Devries, M. C. (2021) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00878.2019 · Cited by 6 · see citing works
Self-citationMinimal alteration in muscle lipid genes following stabilized weight loss
Coker, R. H., Robinette, L., & Kern, P. A. (2017) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2017-0098 · Cited by 3 · see citing works
- Authors
- Devries, M. C., Samjoo, I. A., Hamadeh, M. J., McCready, C., Raha, S., Watt, M. J., Steinberg, G. R., & Tarnopolsky, M. A.
- Affiliations
- McMaster University (CA)
- York University (CA)
- Department of Pediatrics (M.C.D., I.A.S., M.J.H., C.M., S.R., M.A.T.), Ontario L8N 3Z5, Canada
- Monash University (AU)
- Corresponding author
- Tarnopolsky, Mark A.
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2013-12-01
- Volume
- 98
- Issue
- 12
- Pages
- 4852-4862
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2107753327
- Cited by
- 82
- References
- 44
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 1 · 2023: 8 · 2022: 8 · 2021: 9 · 2020: 10 · 2019: 8 · 2018: 9 · 2017: 6 · 2016: 9 · 2015: 3 · 2014: 5
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- McMaster University
- Hospital for Sick Children
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- endurance training, intramyocellular lipid, skeletal muscle, obesity, insulin resistance, mitochondrial function, lipid oxidation, lipid metabolism, diacylglycerol, ceramide, mitochondrial ultrastructure, women, sedentary women, vastus lateralis
- MeSH terms
- Adult, Bicycling, Ceramides, Diglycerides, Female, Humans, Insulin Resistance, Middle Aged, Mitochondria, Muscle, Obesity, Oxidative Phosphorylation, Physical Endurance, Sarcoplasmic Reticulum, Thinness, Biomarkers, Exercise, Body Mass Index, Muscle, Skeletal, Lipid Metabolism, Quadriceps Muscle, Young Adult, Mitochondrial Turnover
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
