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Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide
Open accessAbstract
Aims/hypothesisIntramyocellular lipids, including diacylglycerol (DAG) and ceramides, have been linked to insulin resistance. This randomised repeated-measures study examined the effects of diet-induced weight loss (DIWL) and aerobic exercise (EX) on insulin sensitivity and intramyocellular triacylglycerol (IMTG), DAG and ceramide.MethodsSixteen overweight to obese adults (BMI 30.6 ± 0.8; 67.2 ± 4.0 years of age) with either impaired fasting glucose, or impaired glucose tolerance completed one of two lifestyle interventions: DIWL (n = 8) or EX (n = 8). Insulin sensitivity was determined using hyperinsulinaemic–euglycaemic clamps. Intramyocellular lipids were measured in muscle biopsies using histochemistry and tandem mass spectrometry.ResultsInsulin sensitivity was improved with DIWL (20.6 ± 4.7%) and EX (19.2 ± 12.9%). Body weight and body fat were decreased by both interventions, with greater decreases in DIWL compared with EX. Muscle glycogen, IMTG content and oxidative capacity were all significantly (p < 0.05) decreased with DIWL and increased with EX. There were decreases in DAG with DIWL (−12.4 ± 14.6%) and EX (−40.9 ± 12.0%). Ceramide decreased with EX (−33.7 ± 11.2%), but not with DIWL. Dihydroceramide was decreased with both interventions. Sphingosine was decreased only with EX. Changes in total DAG, total ceramides and other sphingolipids did not correlate with changes in glucose disposal. Stearoyl-coenzyme A desaturase 1 (SCD1) content was decreased with DIWL (−19.5 ± 8.5%, p < 0.05), but increased with EX (19.6 ± 7.4%, p < 0.05). Diacylglycerol acyltransferase 1 (DGAT1) was unchanged with the interventions.Conclusions/interpretationDiet-induced weight loss and exercise training both improved insulin resistance and decreased DAG, while only exercise decreased ceramides, despite the interventions having different effects on IMTG. These alterations may be mediated through differential changes in skeletal muscle capacity for oxidation and triacylglycerol synthesis.Trial registration:ClinicalTrials.gov NCT00766298Funding:ADA Clinical Research Award (B. H. Goodpaster), NIH R01 AG20128 (B. H. Goodpaster), Obesity and Nutrition Research (1P30DK46204) and Clinical and Translational Research Centers (UL1 RR024153)
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Cites
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
Goodpaster, B. H. (2001) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.86.12.5755 · Cited by 1,194
Self-citationBouchard, C., An, P., Rice, T., Skinner, J. S., Wilmore, J. H., Gagnon, J., Pérusse, L., Leon, A. S., & Rao, D. C. (1999) · Journal of Applied Physiology · doi:10.1152/jappl.1999.87.3.1003 · Cited by 875
Bioactive sphingolipids: metabolism and function
Bartke, N., & Hannun, Y. A. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r800080-jlr200 · Cited by 683
Chavez, J. A., Knotts, T. A., Wang, L.-P., Li, G., Dobrowsky, R. T., Florant, G. L., & Summers, S. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212307200 · Cited by 617
Effects of weight loss on regional fat distribution and insulin sensitivity in obesity.
Goodpaster, B. H., Kelley, D. E., Wing, R. R., Meier, A., & Thaete, F. L. (1999) · Diabetes · doi:10.2337/diabetes.48.4.839 · Cited by 608
Self-citationIntramuscular 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 · cited 3×
“Thus, although weight loss and exercise can both improve insulin sensitivity [7, 16] they may have distinctly different effects on IMCL [6, 9].”
BackgroundMethodSelf-citationTarnopolsky, 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
Schenk, S., & Horowitz, J. F. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30566 · Cited by 407
Phillips, D. I. W., Caddy, S., Ilic, V., Fielding, B. A., Frayn, K. N., Borthwick, A. C., & Taylor, R. (1996) · Metabolism · doi:10.1016/s0026-0495(96)90260-7 · Cited by 390 · cited 1×
“Early evidence from cell culture [3], animal models [4] and human studies [5] strongly suggested that accumulation of intramyocellular triacylglycerol (IMTG) was responsible for insulin resistance of obesity and type 2 diabetes.”
Background
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Physical activity/exercise and diabetes: A position statement of the American Diabetes Association
Colberg, S. R., Sigal, R. J., Yardley, J. E., Riddell, M. C., Dunstan, D. W., Dempsey, P. C., Horton, E. S., Castorino, K., & Tate, D. F. (2016) · Diabetes Care · doi:10.2337/dc16-1728 · Cited by 2,991
Update on the effects of physical activity on insulin sensitivity in humans
Bird, S. R., & Hawley, J. A. (2017) · BMJ Open Sport & Exercise Medicine · doi:10.1136/bmjsem-2016-000143 · Cited by 646
Madeo, F., Carmona-Gutierrez, D., Hofer, S. J., & Kroemer, G. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.018 · Cited by 630
Skeletal Muscle Triglycerides, Diacylglycerols, and Ceramides in Insulin Resistance
Amati, F., Dubé, J. J., Alvarez-Carnero, E., Edreira, M. M., Chomentowski, P., Coen, P. M., Switzer, G. E., Bickel, P. E., Stefanovic-Racic, M., Toledo, F. G. S., et al. (2011) · Diabetes · doi:10.2337/db10-1221 · Cited by 395
Self-citationEctopic fat and insulin resistance: pathophysiology and effect of diet and lifestyle interventions.
Snel, M., Jonker, J. T., Schoones, J., Lamb, H., de Roos, A., Pijl, H., Smit, J. W. A., Meinders, A. E., & Jazet, I. M. (2012) · International Journal of Endocrinology · doi:10.1155/2012/983814 · Cited by 368
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Małkiewicz, M. A., Szarmach, A., Sabisz, A., Cubała, W. J., Szurowska, E., & Winklewski, P. J. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1403-x · Cited by 276
Role of intramyocelluar lipids in human health
Coen, P. M., & Goodpaster, B. H. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.05.009 · Cited by 252
Self-citationShepherd, S. O., Cocks, M., Tipton, K. D., Ranasinghe, A. M., Barker, T. A., Burniston, J. G., Wagenmakers, A. J. M., & Shaw, C. S. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2012.240952 · Cited by 207
Perreault, 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
Targeting fatty acid metabolism to improve glucose metabolism
Stinkens, R., Goossens, G. H., Jocken, J. W. E., & Blaak, E. E. (2015) · Obesity Reviews · doi:10.1111/obr.12298 · Cited by 183
Lipids in Psychiatric Disorders and Preventive Medicine
Schneider, M., Levant, B., Reichel, M., Gulbins, E., Kornhuber, J., & Müller, C. P. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.06.002 · Cited by 175
Activation of AMPKα2 in adipocytes is essential for nicotine-induced insulin resistance in vivo
Wu, Y., Song, P., Zhang, W., Liu, J., Dai, X., Liu, Z., Lu, Q., Ouyang, C., Xie, Z., Zhao, Z., et al. (2015) · Nature Medicine · doi:10.1038/nm.3826 · Cited by 169
Muscle sphingolipids during rest and exercise: a C18:0 signature for insulin resistance in humans
Bergman, B. C., Brozinick, J. T., Strauss, A., Bacon, S., Kerege, A., Bui, H. H., Sanders, P., Siddall, P., Wei, T., Thomas, M. K., et al. (2016) · Diabetologia · doi:10.1007/s00125-015-3850-y · Cited by 148
LIM, C., NUNES, E. A., CURRIER, B. S., MCLEOD, J. C., THOMAS, A. C. Q., & PHILLIPS, S. M. (2022) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000002929 · Cited by 142
Mechanism by Which Caloric Restriction Improves Insulin Sensitivity in Sedentary Obese Adults
Johnson, M. L., Distelmaier, K., Lanza, I. R., Irving, B. A., Robinson, M. M., Konopka, A. R., Shulman, G. I., & Nair, K. S. (2016) · Diabetes · doi:10.2337/db15-0675 · Cited by 129
Noone, J., Mucinski, J. M., DeLany, J. P., Sparks, L. M., & Goodpaster, B. H. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2023.12.025 · Cited by 128
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Kitessa, S., & Abeywardena, M. (2016) · Nutrients · doi:10.3390/nu8080466 · Cited by 98
Granata, C., Caruana, N. J., Botella, J., Jamnick, N. A., Huynh, K., Kuang, J., Janssen, H. A., Reljic, B., Mellett, N. A., Laskowski, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-27153-3 · Cited by 93
Dubé, J. J., Coen, P. M., DiStefano, G., Chacon, A. C., Helbling, N. L., Desimone, M. E., Stafanovic-Racic, M., Hames, K. C., Despines, A. A., Toledo, F. G. S., et al. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00257.2014 · Cited by 83
Self-citationDynamics of skeletal muscle lipid pools
Badin, P.-M., Langin, D., & Moro, C. (2013) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2013.08.001 · Cited by 80
Lim, W. K., Davila, S., Teo, J. X., Yang, C., Pua, C. J., Blöcker, C., Lim, J. Q., Ching, J., Yap, J. J. L., Tan, S. Y., et al. (2018) · PLOS Biology · doi:10.1371/journal.pbio.2004285 · Cited by 70
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
Self-citationThe 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
Revisiting the diacylglycerol-induced insulin resistance hypothesis
Amati, F. (2012) · Obesity Reviews · doi:10.1111/j.1467-789x.2012.01036.x · Cited by 59
Self-citationAre Alterations in Skeletal Muscle Mitochondria a Cause or Consequence of Insulin Resistance?
Genders, A. J., Holloway, G. P., & Bishop, D. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186948 · Cited by 51
Mitochondrial function and diabetes: consequences for skeletal and cardiac muscle metabolism
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Handy, R. M., & Holloway, G. P. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1151389 · Cited by 38
“, the production of reactive lipid intermediates), in addition to the pathological production of mitochondrial-derived ROS independently contribute to impairments in insulin signalling (Summers, 2006; Liu et al., 2007; Timmers et al., 2008; Anderson et al., 2009; Dubé et al., 2011).”
BackgroundJahansouz, C., Serrot, F. J., Frohnert, B. I., Foncea, R. E., Dorman, R. B., Slusarek, B., Leslie, D. B., Bernlohr, D. A., & Ikramuddin, S. (2015) · Obesity Surgery · doi:10.1007/s11695-015-1708-5 · Cited by 32
Zabielski, P., Blachnio-Zabielska, A., Lanza, I. R., Gopala, S., Manjunatha, S., Jakaitis, D. R., Persson, X.-M., Gransee, J., Klaus, K. A., Schimke, J. M., et al. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00610.2012 · Cited by 30
Influence of maximal fat oxidation on long-term weight loss maintenance in humans
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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
Bosma, M. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.03.007 · Cited by 23
Metadata
- Authors
- Dubé, J. J., Amati, F., Toledo, F. G. S., Stefanovic-Racic, M., Rossi, A., Coen, P., & Goodpaster, B. H.
- Venue
- Diabetologia
- Published
- 2011-02-17
- Volume
- 54
- Issue
- 5
- Pages
- 1147-1156
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2024872626
- Cited by
- 271
- References
- 15
- FWCI
- 12.71
- Type
- journal article
- Language
- en
- Open access
- bronze
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