Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid–induced insulin resistance

Schenk, Simon; Horowitz, Jeffrey F.

doi:10.1172/jci30566

Cited by 407Metabolism, Diabetes, and CancerAdipose Tissue and MetabolismAdipokines, Inflammation, and Metabolic Diseases

Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid–induced insulin resistance

Open access

Schenk, Simon, Horowitz, Jeffrey F.·2007·Journal of Clinical Investigation

DOI 10.1172/jci30566PMC PMC1866251

Open this paper in CoChat — free account Open PDF

Abstract

Fatty acid oversupply is a key mediator of skeletal muscle insulin resistance in obesity, primarily via accumulation of fatty acid metabolites and activation of proinflammatory pathways. Herein, we demonstrate that fatty acid-induced insulin resistance in humans is completely prevented the day after 1 session of endurance exercise. Because skeletal muscle is the primary site for systemic glucose disposal and is highly susceptible to impaired insulin action by elevated fatty acid availability, we obtained skeletal muscle samples to investigate possible mechanisms mediating this protective effect of exercise. Prevention of fatty acid-induced insulin resistance after exercise accompanied enhanced skeletal muscle protein expression of key lipogenic enzymes and an increase in muscle triglyceride synthesis. Partitioning more fatty acids toward triglyceride synthesis within muscle reduced the accumulation of fatty acid metabolites and suppressed the proinflammatory response in skeletal muscle, as evidenced by decreased phosphorylation and activation of JNK and increased abundance of inhibitor of NF-kappaB alpha (I kappa B-alpha) and I kappa B-beta. We believe this is the first study to demonstrate that 1 session of exercise completely reverses fatty acid-induced insulin resistance in humans. Reversal of insulin resistance accompanied enhanced lipogenic capacity within skeletal muscle, reduced accumulation of highly bioactive fatty acid metabolites, and suppressed activation of proinflammatory pathways known to impair insulin action.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1172/jci30566

Cites

57 of 57 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

Exercise-induced improvements in insulin sensitivity arise from many different alterations.
“Improvements in insulin sensitivity with exercise are induced by a myriad of alterations (34–37), while our data suggest that improvements in cellular redox status play a prominent role.”
From Defects in mitochondrial efficiency and H2O2 emissions in obese women are restored to a lean phenotype with aerobic exercise training (2015) · cites this paper as [37]
Both short-term and long-term exercise raise muscle levels of glycerolipid biosynthetic enzymes, along with greater IMTG synthesis and content.
“Both acute and chronic exercise induce muscle expression of glycerolipid biosynthetic enzymes, which is coupled to increased IMTG synthesis and content [42,80].”
From Intramuscular triacylglycerol and insulin resistance: guilty as charged or wrongly accused? (2010) · cites this paper as [80]
In humans, one exercise session improved insulin sensitivity alongside higher IMTG and lower muscle DAG, ceramide, and glycogen, measured the next day after lipid perfusion.
“A recent study in humans showed that the insulin sensitizing properties of a single exercise session corresponded with elevated IMTG content and lower muscle levels of DAG, ceramide and muscle glycogen, all measured the day after exercise and following a lipid perfusion [80].”
From Intramuscular triacylglycerol and insulin resistance: guilty as charged or wrongly accused? (2010) · cites this paper as [80]
Increasing fatty acid flux in lean individuals to rates similar to or greater than those in obese individuals, typically by lipid-plus-heparin infusion, induces insulin resistance.
“It is well known that increasing the flux of fatty acids in lean individuals to rates similar to or greater than those seen in obese individuals (typically via a lipid-plus-heparin infusion) induces insulin resistance (46,47).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [47]
Muscle-specific overexpression of Dgat1 and an acute bout of exercise prevent high-fat-diet- and lipid-induced impairments in insulin action together with increased intramuscular triglyceride synthesis, decreased DAG and ceramide accumulation, and reduced activation of nPKC/cPKC, JNK, and/or IKK/NF-κB.
“To this end, muscle-specific overexpression of Dgat1 as well as an acute bout of exercise (which increases mitochondrial GPAT and DGAT1 abundance) prevents HFD-and lipid-induced impairments in insulin action in conjunction with increased IMTG synthesis and decreased DAG and ceramide accumulation as well as reduced activation of nPKC/cPKC, JNK, and/or”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [47]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

1 retracted

Positive and Negative Roles of p85α and p85β Regulatory Subunits of Phosphoinositide 3-Kinase in Insulin Signaling
Ueki, K., Fruman, D. A., Yballe, C. M., Faßhauer, M., Klein, J. C., Asano, T., Cantley, L. C., & Kahn, C. R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305602200 · Cited by 207 · see citing works
Retracted
PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
A central role for JNK in obesity and insulin resistance
Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., & Hotamisligil, G. S. (2002) · Nature · doi:10.1038/nature01137 · Cited by 3,359 · see citing works
Calculation of substrate oxidation rates in vivo from gaseous exchange.
Frayn, K. N. (1983) · Journal of Applied Physiology · doi:10.1152/jappl.1983.55.2.628 · Cited by 2,365 · 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
Reversal of Obesity- and Diet-Induced Insulin Resistance with Salicylates or Targeted Disruption of <i>Ikkβ</i>
Yuan, M., Konstantopoulos, N., Lee, J., Hansen, L., Li, Z.-W., Karin, M., & Shoelson, S. E. (2001) · Science · doi:10.1126/science.1061620 · Cited by 1,884 · see citing works
Mechanism by Which Fatty Acids Inhibit Insulin Activation of Insulin Receptor Substrate-1 (IRS-1)-associated Phosphatidylinositol 3-Kinase Activity in Muscle
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
Lipid-Induced Insulin Resistance in Human Muscle Is Associated With Changes in Diacylglycerol, Protein Kinase C, and IκB-α
Itani, S. I., Ruderman, N. B., Schmieder, F., & Boden, G. (2002) · Diabetes · doi:10.2337/diabetes.51.7.2005 · Cited by 1,390 · see citing works
Effects of free fatty acids on glucose transport and IRS-1–associated phosphatidylinositol 3-kinase activity
Dresner, A., Laurent, D., Marcucci, M., Griffin, M. E., Dufour, S., Cline, G. W., Slezak, L. A., Andersen, D. K., Hundal, R. S., Rothman, D. L., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5001 · Cited by 1,311 · see citing works
Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1 H NMR spectroscopy study
Krssak, M., Falk Petersen, K., Dresner, A., DiPietro, L., Vogel, S. M., Rothman, D. L., Shulman, G. I., & Roden, M. (1999) · Diabetologia · doi:10.1007/s001250051123 · Cited by 1,264 · see citing works
Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes
Goodpaster, B. H. (2001) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.86.12.5755 · Cited by 1,194 · see citing works
Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat
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
Equivalence of the insulin sensitivity index in man derived by the minimal model method and the euglycemic glucose clamp.
Bergman, R. N., Prager, R., Volund, A., & Olefsky, J. M. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112886 · Cited by 772 · see citing works
Increased glucose transport-phosphorylation and muscle glycogen synthesis after exercise training in insulin-resistant subjects
Perseghin, G., Price, T. B., Petersen, K. F., Roden, M., Cline, G. W., Gerow, K., Rothman, D. L., & Shulman, G. I. (1996) · New England Journal of Medicine · doi:10.1056/nejm199610313351804 · Cited by 699 · see citing works
Effects of Acute Changes of Plasma Free Fatty Acids on Intramyocellular Fat Content and Insulin Resistance in Healthy Subjects
Boden, G., Lebed, B., Schatz, M., Homko, C., & Lemieux, S. (2001) · Diabetes · doi:10.2337/diabetes.50.7.1612 · Cited by 597 · see citing works
Palmitate-induced Apoptosis Can Occur through a Ceramide-independent Pathway
Listenberger, L. L., Ory, D. S., & Schaffer, J. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010286200 · Cited by 594 · see citing works
Characterizing the effects of saturated fatty acids on insulin signaling and ceramide and diacylglycerol accumulation in 3T3-L1 adipocytes and C2C12 myotubes
Chavez, J. A., & Summers, S. A. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.08.020 · Cited by 498 · see citing works
Overnight lowering of free fatty acids with Acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects.
Santomauro, A. T., Boden, G., Silva, M. E., Rocha, D. M., Santos, R. F., Ursich, M. J., Strassmann, P. G., & Wajchenberg, B. L. (1999) · Diabetes · doi:10.2337/diabetes.48.9.1836 · Cited by 431 · see citing works
Nuclear Sterol Regulatory Element-binding Proteins Activate Genes Responsible for the Entire Program of Unsaturated Fatty Acid Biosynthesis in Transgenic Mouse Liver
Shimomura, I., Shimano, H., Korn, B. S., Bashmakov, Y. K., & Horton, J. D. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.52.35299 · Cited by 383 · see citing works
A Comparison Between the Minimal Model and the Glucose Clamp in the Assessment of Insulin Sensitivity Across the Spectrum of Glucose Tolerance
Saad, M. F., Anderson, R. L., Laws, A., Watanabe, R. M., Kades, W. W., Chen, Y. D. I., Sands, R. E., Pei, D., Savage, P. J., & Bergman, R. N. (1994) · Diabetes · doi:10.2337/diab.43.9.1114 · Cited by 376 · see citing works
Effects of Intravenous and Dietary Lipid Challenge on Intramyocellular Lipid Content and the Relation With Insulin Sensitivity in Humans
Bachmann, O. P., Dahl, D. B., Brechtel, K., Machann, J., Haap, M., Maier, T., Loviscach, M., Stumvoll, M., Claussen, C. D., Schick, F., et al. (2001) · Diabetes · doi:10.2337/diabetes.50.11.2579 · Cited by 369 · cited 3× · see citing works
“As was found in previous reports (1, 3, 24), we observed that increasing plasma fatty acid concentration approximately 4-fold above basal levels (Figure 2) in SED subjects, via an overnight infusion of lipid-plus-heparin, impaired insulin sensitivity index (Si) by approximately 30% the next day (Figure 3).”
BackgroundResult
Effect of exercise on insulin action in human skeletal muscle
Richter, E. A., Mikines, K. J., Galbo, H., & Kiens, B. (1989) · Journal of Applied Physiology · doi:10.1152/jappl.1989.66.2.876 · Cited by 357 · see citing works
Effects of low-intensity prolonged exercise on PGC-1 mRNA expression in rat epitrochlearis muscle
Terada, S., Goto, M., Kato, M., Kawanaka, K., Shimokawa, T., & Tabata, I. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00881-1 · Cited by 354 · see citing works
Regulation of 5′AMP-activated protein kinase activity and substrate utilization in exercising human skeletal muscle
Wojtaszewski, J. F. P., MacDonald, C., Nielsen, J. N., Hellsten, Y., Hardie, D. G., Kemp, B. E., Kiens, B., & Richter, E. A. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00436.2002 · Cited by 348 · see citing works
Prolonged increase in insulin-stimulated glucose transport in muscle after exercise
Cartee, G. D., Young, D. A., Sleeper, M. D., Zierath, J., Wallberg-Henriksson, H., & Holloszy, J. O. (1989) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1989.256.4.e494 · Cited by 342 · see citing works
Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites
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
Reduced expression of the murine p85α subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes
Mauvais‐Jarvis, F., Ueki, K., Fruman, D. A., Hirshman, M. F., Sakamoto, K., Goodyear, L. J., Iannacone, M., Accili, D., Cantley, L. C., & Kahn, C. R. (2002) · Journal of Clinical Investigation · doi:10.1172/jci13305 · Cited by 245 · see citing works
Identification of Glycerol-3-phosphate Acyltransferase as an Adipocyte Determination and Differentiation Factor 1- and Sterol Regulatory Element-binding Protein-responsive Gene
Ericsson, J., Jackson, S. M., Kim, J. B., Spiegelman, B. M., & Edwards, P. A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.11.7298 · Cited by 229 · see citing works
Modified protocols improve insulin sensitivity estimation using the minimal model
Yang, Y. J., Youn, J. H., & Bergman, R. N. (1987) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1987.253.6.e595 · Cited by 212 · see citing works
Increased p85/55/50 Expression and Decreased Phosphotidylinositol 3-Kinase Activity in Insulin-Resistant Human Skeletal Muscle
Bandyopadhyay, G. K., Yu, J. G., Ofrecio, J., & Olefsky, J. M. (2005) · Diabetes · doi:10.2337/diabetes.54.8.2351 · Cited by 210 · see citing works
Effects of Prior High-Intensity Exercise on Glucose Metabolism in Normal and Insulin-resistant Men
Devlin, J. T., & Horton, E. S. (1985) · Diabetes · doi:10.2337/diab.34.10.973 · Cited by 207 · see citing works
Reversal of diet‐induced insulin resistance with a single bout of exercise in the rat: the role of PTP1B and IRS‐1 serine phosphorylation
Ropelle, E. R., Pauli, J. R., Prada, P. O., de Souza, C. T., Picardi, P. K., Faria, M. C., Cintra, D. E., Fernandes, M. F. D. A., Flores, M. B. S., Velloso, L. A., et al. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.120006 · Cited by 187 · see citing works
Diet-Induced Muscle Insulin Resistance in Rats Is Ameliorated by Acute Dietary Lipid Withdrawal or a Single Bout of Exercise: Parallel Relationship Between Insulin Stimulation of Glucose Uptake and Suppression of Long-Chain Fatty Acyl-CoA
Oakes, N. D., Bell-Anderson, K. S., Furler, S. M., Camilleri, S., Saha, A. K., Ruderman, N. B., Chisholm, D. J., & Kraegen, E. W. (1997) · Diabetes · doi:10.2337/diab.46.12.2022 · Cited by 176 · see citing works
Postexercise fat intake repletes intramyocellular lipids but no faster in trained than in sedentary subjects
Décombaz, J., Schmitt, B., Ith, M., Decarli, B., Diem, P., Kreis, R., Hoppeler, H. H., & Boesch, C. (2001) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.281.3.r760 · Cited by 154 · see citing works
Effect of short-term fasting on lipid kinetics in lean and obese women
Horowitz, J. F., Coppack, S. W., Paramore, D. S., Cryer, P. E., Zhao, G., & Klein, S. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.276.2.e278 · Cited by 149 · see citing works
Self-citation
Reduced Skeletal Muscle Inhibitor of κBβ Content Is Associated With Insulin Resistance in Subjects With Type 2 Diabetes
Sriwijitkamol, A., Christ-Roberts, C. Y., Berria, R., Eagan, P. A., Pratipanawatr, T., DeFronzo, R. A., Mandarino, L. J., & Musi, N. (2006) · Diabetes · doi:10.2337/diabetes.55.03.06.db05-0677 · Cited by 144 · see citing works
Dissociation of AMPK activity and ACCβ phosphorylation in human muscle during prolonged exercise
Wojtaszewski, J. F. P., Mourtzakis, M., Hillig, T., Saltin, B., & Pilegaard, H. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)02465-8 · Cited by 126 · see citing works
Skeletal muscle fat and carbohydrate metabolism during recovery from glycogen-depleting exercise in humans
Kimber, N. E., Heigenhauser, G. J. F., Spriet, L. L., & Dyck, D. J. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2002.031179 · Cited by 107 · see citing works
Stearoyl CoA desaturase 1 is elevated in obesity but protects against fatty acid-induced skeletal muscle insulin resistance in vitro
Pinnamaneni, S. K., Southgate, R. J., Febbraio, M. A., & Watt, M. J. (2006) · Diabetologia · doi:10.1007/s00125-006-0427-9 · Cited by 99 · see citing works
Mitochondrial Glycerol Phosphate Acyltransferase Directs the Incorporation of Exogenous Fatty Acids into Triacylglycerol
Igal, R. A., Wang, S., González-Baró, M. R., & Coleman, R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103386200 · Cited by 97 · see citing works
Up-regulation of SREBP-1c and lipogenic genes in skeletal muscles after exercise training
Ikeda, S., Miyazaki, H., Nakatani, T., Kai, Y., Kamei, Y., Miura, S., Tsuboyama-Kasaoka, N., & Ezaki, O. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00883-5 · Cited by 92 · see citing works
A comparison between the minimal model and the glucose clamp in the assessment of insulin sensitivity across the spectrum of glucose tolerance. Insulin Resistance Atherosclerosis Study
Saad, M. F., Anderson, R. L., Laws, A., et al. (1994) · Diabetes · doi:10.2337/diabetes.43.9.1114 · Cited by 91 · see citing works
Ciliary Neurotrophic Factor Prevents Acute Lipid-Induced Insulin Resistance by Attenuating Ceramide Accumulation and Phosphorylation of c-Jun N-Terminal Kinase in Peripheral Tissues
Watt, M. J., Hevener, A. L., Lancaster, G. I., & Febbraio, M. A. (2006) · Endocrinology · doi:10.1210/en.2005-1074 · Cited by 87 · see citing works
Thiazolidinedione Treatment Prevents Free Fatty Acid–Induced Insulin Resistance in Male Wistar Rats
Hevener, A. L., Reichart, D. R., Janež, A., & Olefsky, J. M. (2001) · Diabetes · doi:10.2337/diabetes.50.10.2316 · Cited by 78 · see citing works
Role of glycogen-lowering exercise in the change of fat oxidation in response to a high-fat diet.
Schrauwen, P., Lichtenbelt, W. D. V. M., Saris, W. H. M., & Westerterp, K. R. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.273.3.e623 · Cited by 77 · see citing works
Effect of prior exercise on the partitioning of an intestinal glucose load between splanchnic bed and skeletal muscle.
Hamilton, K. S., Gibbons, F. K., Bracy, D. P., Lacy, D. B., Cherrington, A. D., & Wasserman, D. H. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118756 · Cited by 75 · see citing works
Overexpression of Diacylglycerol Acyltransferase-1 Reduces Phospholipid Synthesis, Proliferation, and Invasiveness in Simian Virus 40-transformed Human Lung Fibroblasts
Bagnato, C., & Igal, R. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305760200 · Cited by 72 · see citing works
Fat balance in obese subjects: role of glycogen stores
Schrauwen, P., Lichtenbelt, W. D. V. M., Saris, W. H. M., & Westerterp, K. R. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.274.6.e1027 · Cited by 72 · see citing works
Insulin signalling: effects of prior exercise
Wojtaszewski, J. F. P., Jørgensen, S. B., Frøsig, C., MacDonald, C., Birk, J. B., & Richter, E. A. (2003) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.2003.01151.x · Cited by 68 · see citing works
Thiazolidinediones enhance skeletal muscle triacylglycerol synthesis while protecting against fatty acid-induced inflammation and insulin resistance
Todd, M. K., Watt, M. J., Le, J., Hevener, A. L., & Turcotte, L. P. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00080.2006 · Cited by 58 · see citing works
Exercise training and calorie restriction increase SREBP-1 expression and intramuscular triglyceride in skeletal muscle
Nadeau, K. J., Ehlers, L. B., Aguirre, L. E., Moore, R. L., Jew, K. N., Ortmeyer, H. K., Hansen, B. C., Reusch, J. E. B., & Draznin, B. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00543.2005 · Cited by 57 · see citing works
Postexercise insulin sensitivity is not impaired after an overnight lipid infusion
Schenk, S., Cook, J. N., Kaufman, A. E., & Horowitz, J. F. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00401.2004 · Cited by 55 · see citing works
Self-citation
Prior exercise increases subsequent utilization of dietary fat
Votruba, S. B., Atkinson, R. L., Hirvonen, M. D., & Schoeller, D. A. (2002) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-200211000-00011 · Cited by 51 · see citing works
Adding fat calories to meals after exercise does not alter glucose tolerance
Fox, A. K., Kaufman, A. E., & Horowitz, J. F. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01398.2003 · Cited by 46 · see citing works
Self-citation
DGAT1 overexpression in muscle by in vivo DNA electroporation increases intramyocellular lipid content
Roorda, B. D., Hesselink, M. K. C., Schaart, G., Moonen‐Kornips, E., Martínez‐Martínez, P., Losen, M. H., Baets, M. H. D., Mensink, R. P., & Schrauwen, P. (2004) · Journal of Lipid Research · doi:10.1194/jlr.m400416-jlr200 · Cited by 45 · see citing works
Reduced expression of the murine p85α subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes
Mauvais‐Jarvis, F., Ueki, K., Fruman, D. A., Hirshman, M. F., Sakamoto, K., Goodyear, L. J., Iannacone, M., Accili, D., Cantley, L. C., & Kahn, C. R. (2002) · Journal of Clinical Investigation · doi:10.1172/jci200213305 · Cited by 17 · see citing works

Flagged first, then by citations

Sorted by citations

Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association
Kernan, W. N., Ovbiagele, B., Black, H. R., Bravata, D. M., Chimowitz, M. I., Ezekowitz, M. D., Fang, M. C., Fisher, M., Furie, K. L., Heck, D. V., et al. (2014) · Stroke · doi:10.1161/str.0000000000000024 · Cited by 5,170 · see citing works
Lack of Exercise Is a Major Cause of Chronic Diseases
Booth, F. W., Roberts, C. K., & Laye, M. J. (2012) · Comprehensive Physiology · doi:10.1002/cphy.c110025 · Cited by 2,575 · see citing works
Exercise Metabolism and the Molecular Regulation of Skeletal Muscle Adaptation
Egan, B., & Zierath, J. R. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.012 · Cited by 2,084 · see citing works
The PI3K/AKT Pathway in Obesity and Type 2 Diabetes
Huang, X., Liu, G., Guo, J., & Su, Z. (2018) · International Journal of Biological Sciences · doi:10.7150/ijbs.27173 · Cited by 1,673 · see citing works
“In early studies, insulin resistance was thought to be accompanied by excessive intramyocellular lipid (IMCL) levels [49], and improved insulin sensitivity observed in subjects with T2DM by reduced IMCL levels [50].”
Background
Lipid Droplets and Cellular Lipid Metabolism
Walther, T. C., & Farese, R. V. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061009-102430 · Cited by 1,668 · see citing works
Insulin sensitivity: Modulation by nutrients and inflammation
Schenk, S., Saberi, M., & Olefsky, J. M. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34260 · Cited by 1,191 · see citing works
Self-citation
Lipid-induced insulin resistance: unravelling the mechanism
Samuel, V. T., Petersen, K. F., & Shulman, G. I. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60408-4 · Cited by 1,189 · see citing works
Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: The central role of nontriglyceride fatty acid metabolites†
Neuschwander‐Tetri, B. A. (2010) · Hepatology · doi:10.1002/hep.23719 · Cited by 1,077 · see citing works
Structure and function of the skeletal muscle extracellular matrix
Gillies, A. R., & Lieber, R. L. (2011) · Muscle & Nerve · doi:10.1002/mus.22094 · Cited by 1,023 · see citing works
Obesity, insulin resistance and free fatty acids
Boden, G. (2011) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0b013e3283444b09 · Cited by 848 · see citing works
Cardiac Metabolism and its Interactions With Contraction, Growth, and Survival of Cardiomyocytes
Kolwicz, S. C., Purohit, S., & Tian, R. (2013) · Circulation Research · doi:10.1161/circresaha.113.302095 · Cited by 810 · see citing works
Mechanisms of insulin resistance in obesity
Ye, J. (2013) · Frontiers of Medicine · doi:10.1007/s11684-013-0262-6 · Cited by 699 · see citing works
Stroke Epidemiology and Risk Factor Management
Guzik, A. K., & Bushnell, C. (2017) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000000416 · Cited by 654 · see citing works
A Ceramide-Centric View of Insulin Resistance
Chavez, J. A., & Summers, S. A. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.002 · Cited by 617 · see citing works
Resistance exercise reduces liver fat and its mediators in non-alcoholic fatty liver disease independent of weight loss
Hallsworth, K., Fattakhova, G., Hollingsworth, K. G., Thoma, C., Moore, S., Taylor, R., Day, C. P., & Trenell, M. I. (2011) · Gut · doi:10.1136/gut.2011.242073 · Cited by 529 · see citing works
Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism
Flowers, M. T., & Ntambi, J. M. (2008) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3282f9b54d · Cited by 438 · see citing works
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 · see citing works
Lack of Exercise Is a Major Cause of Chronic Diseases
Booth, F. W., Roberts, C. K., & Laye, M. J. (2012) · Comprehensive physiology · doi:10.1002/j.2040-4603.2012.tb00425.x · Cited by 397 · see citing works
Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete's paradox revisited
Dubé, J. J., Amati, F., Stefanovic-Racic, M., Toledo, F. G. S., Sauers, S. E., & Goodpaster, B. H. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00769.2007 · Cited by 378 · see citing works
Evolving Concepts in the Pathogenesis of NASH: Beyond Steatosis and Inflammation
Peverill, W., Powell, L. W., & Skoien, R. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15058591 · Cited by 379 · see citing works
Lipid Droplets in Cancer: Guardians of Fat in a Stressful World
Petan, T., Jovičić, E. J., & Jusović, M. (2018) · Molecules · doi:10.3390/molecules23081941 · Cited by 369 · see citing works
Restoration of Muscle Mitochondrial Function and Metabolic Flexibility in Type 2 Diabetes by Exercise Training Is Paralleled by Increased Myocellular Fat Storage and Improved Insulin Sensitivity
Meex, R. C. R., Schrauwen-Hinderling, V. B., Moonen-Kornips, E., Schaart, G., Mensink, M., Phielix, E., van de Weijer, T., Sels, J.-P., Schrauwen, P., & Hesselink, M. K. C. (2010) · Diabetes · doi:10.2337/db09-1322 · Cited by 355 · see citing works
Oleate Reverses Palmitate-induced Insulin Resistance and Inflammation in Skeletal Muscle Cells
Coll, T., Eyre, E., Rodríguez-Calvo, R., Palomer, X., Sánchez, R. M., Merlos, M., Laguna, J. C., & Vázquez-Carrera, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708700200 · Cited by 347 · see citing works
The effects of physical exercise on fatty liver disease.
van der Windt, D. J., Sud, V., Zhang, H., Tsung, A., & Huang, H. (2018) · Gene Expression · doi:10.3727/105221617x15124844266408 · Cited by 294 · see citing works
Different effects of oleate vs. palmitate on mitochondrial function, apoptosis, and insulin signaling in L6 skeletal muscle cells: role of oxidative stress
Yuzefovych, L., Wilson, G., & Rachek, L. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00238.2010 · Cited by 280 · see citing works
Metabolic flexibility in the development of insulin resistance and type 2 diabetes: effects of lifestyle
Corpeleijn, E., Saris, W. H. M., & Blaak, E. E. (2009) · Obesity Reviews · doi:10.1111/j.1467-789x.2008.00544.x · Cited by 280 · see citing works
Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide
Dubé, J. J., Amati, F., Toledo, F. G. S., Stefanović-Račić, M., Rossi, A. P., Coen, P. M., & Goodpaster, B. H. (2011) · Diabetologia · doi:10.1007/s00125-011-2065-0 · Cited by 272 · see citing works
Insights into Stearoyl-CoA Desaturase-1 Regulation of Systemic Metabolism
Aljohani, A., Syed, D. N., & Ntambi, J. M. (2017) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2017.10.003 · Cited by 271 · see citing works
Molecular Responses to Acute Exercise and Their Relevance for Adaptations in Skeletal Muscle to Exercise Training
Egan, B., & Sharples, A. P. (2023) · Physiological Reviews · doi:10.1152/physrev.00054.2021 · Cited by 278 · see citing works
Role of fatty acid uptake and fatty acid β-oxidation in mediating insulin resistance in heart and skeletal muscle
Zhang, L., Keung, W., Samokhvalov, V., Wang, W. J., & Lopaschuk, G. D. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.09.014 · Cited by 257 · see citing works
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 · see citing works
DGAT1 Expression Increases Heart Triglyceride Content but Ameliorates Lipotoxicity
Liu, L., Shi, X., Bharadwaj, K. G., Ikeda, S., Yamashita, H., Yagyu, H., Schaffer, J. E., Yu, Y., & Goldberg, I. J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.049817 · Cited by 240 · see citing works
Stearoyl CoA Desaturase 1: Role in Cellular Inflammation and Stress
Liu, X., Strable, M. S., & Ntambi, J. M. (2011) · Advances in Nutrition · doi:10.3945/an.110.000125 · Cited by 218 · see citing works
Stearoyl-CoA desaturase: rogue or innocent bystander?
Hodson, L., & Fielding, B. A. (2012) · Progress in Lipid Research · doi:10.1016/j.plipres.2012.08.002 · Cited by 215 · see citing works
Skeletal muscle insulin resistance: roles of fatty acid metabolism and exercise
Turcotte, L. P., & Fisher, J. S. (2008) · Physical Therapy · doi:10.2522/ptj.20080018 · Cited by 209 · see citing works
Sprint interval and traditional endurance training increase net intramuscular triglyceride breakdown and expression of perilipin 2 and 5
Shepherd, 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 · see citing works
Free fatty acids and skeletal muscle insulin resistance
Kraegen, E. W., & Cooney, G. J. (2008) · Current Opinion in Lipidology · doi:10.1097/01.mol.0000319118.44995.9a · Cited by 206 · see citing works
Moderate-Intensity Exercise and High-Intensity Interval Training Affect Insulin Sensitivity Similarly in Obese Adults
Ryan, B. J., Schleh, M. W., Ahn, C., Ludzki, A. C., Gillen, J. B., Varshney, P., Pelt, D. W. V., Pitchford, L. M., Chenevert, T. L., Gioscia‐Ryan, R. A., et al. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa345 · Cited by 206 · see citing works
Self-citation
Effects of Exercise Training Intensity on Pancreatic β-Cell Function
Slentz, C. A., Tanner, C. J., Bateman, L. A., Durheim, M. T., Huffman, K. M., Houmard, J. A., & Kraus, W. E. (2009) · Diabetes Care · doi:10.2337/dc09-0032 · Cited by 192 · see citing works
Short‐term sprint interval training increases insulin sensitivity in healthy adults but does not affect the thermogenic response to β‐adrenergic stimulation
Richards, J. C., Johnson, T. K., Kuzma, J. N., Lonac, M. C., Schweder, M. M., Voyles, W. F., & Bell, C. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.189886 · Cited by 187 · see citing works
Lipid droplet proteins and metabolic diseases
Xu, S., Zhang, X., & Liu, P. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.07.019 · Cited by 185 · see citing works
Intramuscular lipid metabolism, insulin action, and obesity
Consitt, L. A., Bell, J. A., & Houmard, J. A. (2009) · IUBMB Life · doi:10.1002/iub.142 · Cited by 180 · see citing works
Determinants of intramyocellular triglyceride turnover: implications for insulin sensitivity
Moro, C., Bajpeyi, S., & Smith, S. R. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00624.2007 · Cited by 179 · see citing works
Muscular diacylglycerol metabolism and insulin resistance
Timmers, S., Schrauwen, P., & den Bosch, J. D. V. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.12.002 · Cited by 159 · see citing works
Localisation and composition of skeletal muscle diacylglycerol predicts insulin resistance in humans
Bergman, B. C., Hunerdosse, D. M., Kerege, A. A., Playdon, M. C., & Perreault, L. (2012) · Diabetologia · doi:10.1007/s00125-011-2419-7 · Cited by 159 · see citing works
Obesity Impairs Skeletal Muscle Regeneration Through Inhibition of AMPK
Fu, X., Zhu, M., Zhang, S., Foretz, M., Viollet, B., & Du, M. (2016) · Diabetes · doi:10.2337/db15-0647 · Cited by 155 · see citing works
Perilipin 2 improves insulin sensitivity in skeletal muscle despite elevated intramuscular lipid levels
Bosma, M., Hesselink, M. K. C., Sparks, L. M., Timmers, S., Ferraz, M. J., Mattijssen, F., van Beurden, D., Schaart, G., de Baets, M. H., Verheyen, F. K., et al. (2012) · Diabetes · doi:10.2337/db11-1402 · Cited by 149 · see citing works
Role of Peroxisome Proliferator-activated Receptor δ/β in Hepatic Metabolic Regulation
Liu, S., Hatano, B., Zhao, M., Yen, C.-C., Kang, K., Reilly, S. M., Gangl, M. R., Görgün, C. Z., Balschi, J. A., Ntambi, J. M., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.138115 · Cited by 151 · see citing works
Individual Stearoyl-CoA Desaturase 1 Expression Modulates Endoplasmic Reticulum Stress and Inflammation in Human Myotubes and Is Associated With Skeletal Muscle Lipid Storage and Insulin Sensitivity In Vivo
Peter, A., Weigert, C., Staiger, H., Machicao, F. E., Schick, F., Machann, J., Stefan, N., Thamer, C., Häring, H., & Schleicher, E. D. (2009) · Diabetes · doi:10.2337/db09-0188 · Cited by 152 · see citing works
Excess of free fatty acids as a cause of metabolic dysfunction in skeletal muscle
TUMOVA, J., ANDEL, M., & TRNKA, J. (2016) · Physiological Research · doi:10.33549/physiolres.932993 · Cited by 143 · see citing works
Skeletal muscle energy metabolism in obesity
Mengeste, A. M., Rustan, A. C., & Lund, J. (2021) · Obesity · doi:10.1002/oby.23227 · Cited by 141 · see citing works
AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice
O'Neill, H., Lally, J., Galic, S., Thomas, M. M., Azizi, P. D., Fullerton, M., Smith, B. K., Pulinilkunnil, T., Chen, Z.-P., Samaan, M., et al. (2014) · Diabetologia · doi:10.1007/s00125-014-3273-1 · Cited by 140 · see citing works
Lipid metabolism in skeletal muscle: generation of adaptive and maladaptive intracellular signals for cellular function
Watt, M. J., & Hoy, A. J. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00561.2011 · Cited by 142 · see citing works
Obesity
Kernan, W. N., Inzucchi, S. E., Sawan, C., Macko, R. F., & Furie, K. L. (2012) · Stroke · doi:10.1161/strokeaha.111.639922 · Cited by 143 · see citing works
Mechanisms for greater insulin-stimulated glucose uptake in normal and insulin-resistant skeletal muscle after acute exercise
Cartee, G. D. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00416.2015 · Cited by 140 · see citing works
Efficacy of increased resistant starch consumption in human type 2 diabetes
Bodinham, C. L., Smith, L., Thomas, E. L., Bell, J. D., Swann, J. R., Costabile, A., Russell-Jones, D. L., Umpleby, A. M., & Robertson, M. D. (2014) · Endocrine Connections · doi:10.1530/ec-14-0036 · Cited by 139 · see citing works
Intramuscular triacylglycerol and insulin resistance: guilty as charged or wrongly accused?
Muoio, D. M. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.11.007 · Cited by 137 · see citing works
Getting the message across: mechanisms of physiological cross talk by adipose tissue
Lee, D.-E., Kehlenbrink, S., Lee, H., Hawkins, M. A., & Yudkin, J. S. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00015.2009 · Cited by 137 · see citing works
Adipose triglyceride lipase in human skeletal muscle is upregulated by exercise training
Alsted, T. J., Nybo, L., Schweiger, M., Fledelius, C., Jacobsen, P., Zimmermann, R., Zechner, R., & Kiens, B. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90912.2008 · Cited by 135 · see citing works
Re-evaluating lipotoxic triggers in skeletal muscle: Relating intramyocellular lipid metabolism to insulin sensitivity
Bosma, M., Kersten, S., Hesselink, M. K. C., & Schrauwen, P. (2011) · Progress in Lipid Research · doi:10.1016/j.plipres.2011.11.003 · Cited by 134 · see citing works
Overexpression of PLIN5 in skeletal muscle promotes oxidative gene expression and intramyocellular lipid content without compromising insulin sensitivity
Bosma, M., Sparks, L. M., Hooiveld, G. J. E. J., Jörgensen, J. A., Houten, S. M., Schrauwen, P., Kersten, S., & Hesselink, M. K. C. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.01.007 · Cited by 135 · see citing works
Altered Skeletal Muscle Lipase Expression and Activity Contribute to Insulin Resistance in Humans
Badin, P.-M., Louche, K., Mairal, A., Liebisch, G., Schmitz, G., Rustan, A. C., Smith, S. R., Langin, D., & Moro, C. (2011) · Diabetes · doi:10.2337/db10-1364 · Cited by 132 · see citing works
Effects of exercise training alone vs a combined exercise and nutritional lifestyle intervention on glucose homeostasis in prediabetic individuals: a randomised controlled trial
Slentz, C. A., Bateman, L. A., Willis, L. H., Granville, E., Piner, L. W., Samsa, G. P., Setji, T. L., Muehlbauer, M. J., Huffman, K. M., Bales, C. W., et al. (2016) · Diabetologia · doi:10.1007/s00125-016-4051-z · Cited by 130 · see citing works
Contribution of specific ceramides to obesity-associated metabolic diseases
Hammerschmidt, P., & Brüning, J. C. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04401-3 · Cited by 128 · see citing works
The Effect of Exercise and Nutrition on Intramuscular Fat Metabolism and Insulin Sensitivity
Shaw, C. S., Clark, J., & Wagenmakers, A. J. M. (2010) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.012809.104817 · Cited by 128 · see citing works
High-intensity interval versus moderate-intensity continuous training: Superior metabolic benefits in diet-induced obesity mice
Wang, N., Liu, Y., Ma, Y., & Wen, D. (2017) · Life Sciences · doi:10.1016/j.lfs.2017.08.023 · Cited by 125 · see citing works
Muscle-specific 4E-BP1 signaling activation improves metabolic parameters during aging and obesity
Tsai, S., Sitzmann, J. M., Dastidar, S. G., Rodriguez, A. A., Vu, S. L., McDonald, C. E., Academia, E. C., O’Leary, M. N., Ashe, T. D., Spada, A. R. L., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci77361 · Cited by 130 · see citing works
Improved insulin sensitivity after weight loss and exercise training is mediated by a reduction in plasma fatty acid mobilization, not enhanced oxidative capacity
Schenk, S., Harber, M. P., Shrivastava, C. R., Burant, C., & Horowitz, J. F. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.175489 · Cited by 123 · see citing works
Self-citation
Endurance exercise training ameliorates insulin resistance and reticulum stress in adipose and hepatic tissue in obese rats
da Luz, G., Frederico, M. J. S., da Silva, S., Vitto, M. F., Cesconetto, P. A., Pinho, R. A., Pauli, J. R., da Silva, A. S. R., Cintra, D. E., Ropelle, E. R., et al. (2011) · European Journal of Applied Physiology · doi:10.1007/s00421-010-1802-2 · Cited by 119 · see citing works
Adipose Triglyceride Lipase-Null Mice Are Resistant to High-Fat Diet–Induced Insulin Resistance Despite Reduced Energy Expenditure and Ectopic Lipid Accumulation
Hoy, A. J., Bruce, C. R., Turpin-Nolan, S. M., Morris, A. J., Febbraio, M. A., & Watt, M. J. (2010) · Endocrinology · doi:10.1210/en.2010-0661 · Cited by 117 · see citing works
Origins of metabolic complications in obesity
Mittendorfer, B. (2011) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32834ad8b6 · Cited by 116 · see citing works
BNIP3L/Nix-induced mitochondrial fission, mitophagy, and impaired myocyte glucose uptake are abrogated by PRKA/PKA phosphorylation
da Silva Rosa, S. C., Martens, M. D., Field, J. T., Nguyen, L., Kereliuk, S. M., Hai, Y., Chapman, D., Diehl-Jones, W., Aliani, M., West, A. R., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1821548 · Cited by 117 · see citing works
Hepatic triacylglycerol synthesis and secretion: DGAT2 as the link between glycaemia and triglyceridaemia
Zammit, V. A. (2013) · Biochemical Journal · doi:10.1042/bj20121689 · Cited by 115 · see citing works
Increased basal level of Akt-dependent insulin signaling may be responsible for the development of insulin resistance
Liu, H.-Y., Hong, T., Wen, G.-B., Han, J., Zuo, D., Liu, Z., & Cao, W. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00374.2009 · Cited by 111 · see citing works
Defects in mitochondrial efficiency and H2O2 emissions in obese women are restored to a lean phenotype with aerobic exercise training
Konopka, A. R., Asante, A., Lanza, I. R., Robinson, M. M., Johnson, M. L., Dalla Man, C., Cobelli, C., Amols, M. H., Irving, B. A., & Nair, K. S. (2015) · Diabetes · doi:10.2337/db14-1701 · Cited by 112 · see citing works
MECHANISMS IN ENDOCRINOLOGY: Skeletal muscle lipotoxicity in insulin resistance and type 2 diabetes: a causal mechanism or an innocent bystander?
Brøns, C., & Grunnet, L. G. (2016) · European Journal of Endocrinology · doi:10.1530/eje-16-0488 · Cited by 109 · see citing works
A Single Session of Low-Intensity Exercise Is Sufficient to Enhance Insulin Sensitivity Into the Next Day in Obese Adults
Newsom, S. A., Everett, A. C., Hinko, A., & Horowitz, J. F. (2013) · Diabetes Care · doi:10.2337/dc12-2606 · Cited by 110 · see citing works
Self-citation
Training in the fasted state improves glucose tolerance during fat-rich diet
Proeyen, K. V., Szlufcik, K., Nielens, H., Pelgrim, K., Deldicque, L., Hesselink, M. K. C., Veldhoven, P. P. V., & Hespel, P. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.196493 · Cited by 106 · see citing works
Sequestration of fatty acids in triglycerides prevents endoplasmic reticulum stress in an in vitro model of cardiomyocyte lipotoxicity
Bosma, M., Dapito, D. H., Drosatos-Tampakaki, Z., Son, N. H., Huang, L., Kersten, S., Drosatos, K., & Goldberg, I. J. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.09.012 · Cited by 104 · see citing works
The ontogeny of aerobic and diving capacity in the skeletal muscles of Weddell seals
Kanatous, S. B., Hawke, T. J., Trumble, S. J., Pearson, L. E., Watson, R. R., Garry, D. J., Williams, T. M., & Davis, R. W. (2008) · Journal of Experimental Biology · doi:10.1242/jeb.018119 · Cited by 104 · see citing works
Increased intramuscular lipid synthesis and low saturation relate to insulin sensitivity in endurance-trained athletes
Bergman, B. C., Perreault, L., Hunerdosse, D. M., Koehler, M. C., Samek, A. M., & Eckel, R. H. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00684.2009 · Cited by 103 · see citing works
Exercise Alleviates Lipid-Induced Insulin Resistance in Human Skeletal Muscle–Signaling Interaction at the Level of TBC1 Domain Family Member 4
Pehmøller, C. K., Brandt, N., Birk, J. B., Høeg, L. D., Sjøberg, K. A., Goodyear, L. J., Kiens, B., Richter, E. A., & Wojtaszewski, J. F. P. (2012) · Diabetes · doi:10.2337/db11-1572 · Cited by 103 · see citing works
Short-Term Exercise Improves β-Cell Function and Insulin Resistance in Older People with Impaired Glucose Tolerance
Bloem, C. J., & Chang, A. M. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1734 · Cited by 103 · see citing works
High Oxidative Capacity Due to Chronic Exercise Training Attenuates Lipid-Induced Insulin Resistance
Phielix, E., Meex, R., Ouwens, D. M., Sparks, L., Hoeks, J., Schaart, G., Moonen-Kornips, E., Hesselink, M. K. C., & Schrauwen, P. (2012) · Diabetes · doi:10.2337/db11-1832 · Cited by 99 · see citing works
“In that respect, it was recently shown that one bout of acute exercise was able to prevent lipid-induced IR by the efficient shuttling of fatty acids in the muscle into inert triglyceride stores, through activation of diacylglycerol acyltransferase (DGAT) (41).”
Background
Increased lipid accumulation and insulin resistance in transgenic mice expressing DGAT2 in glycolytic (type II) muscle
Levin, M. C., Monetti, M., Watt, M. J., Sajan, M. P., Stevens, R. D., Bain, J. R., Newgard, C. B., Farese, R. V., & Farese, R. V. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00158.2007 · Cited by 99 · see citing works
AMP-activated Protein Kinase Stimulates Warburg-like Glycolysis and Activation of Satellite Cells during Muscle Regeneration
Fu, X., Zhu, M. J., Dodson, M. V., & Du, ‬. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.665232 · Cited by 96 · see citing works
Acute physical exercise reverses <i>S</i>‐nitrosation of the insulin receptor, insulin receptor substrate 1 and protein kinase B/Akt in diet‐induced obese Wistar rats
Pauli, J. R., Ropelle, E. R., Cintra, D. E., Carvalho‐Filho, M. A., Moraes, J. C., De Souza, C. T., Velloso, L. A., Carvalheira, J. B. C., & Saad, M. J. A. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2007.142414 · Cited by 97 · see citing works
PPARγ coactivator-1α contributes to exercise-induced regulation of intramuscular lipid droplet programming in mice and humans
Koves, T. R., Sparks, L. M., Kovalik, J., Mosedale, M., Arumugam, R., DeBalsi, K. L., Everingham, K., Thorne, L. B., Esther Phielix, E., Meex, R. C. R., et al. (2012) · Journal of Lipid Research · doi:10.1194/jlr.p028910 · Cited by 95 · see citing works
Targeting ceramide metabolism in obesity.
Aburasayn, H., Batran, R. A., & Ussher, J. (2016) · American Journal of Physiology. Endocrinology and Metabolism · doi:10.1152/ajpendo.00133.2016 · Cited by 94 · see citing works
Lipid droplet dynamics in skeletal muscle
Bosma, M. (2016) · Experimental Cell Research · doi:10.1016/j.yexcr.2015.10.023 · Cited by 91 · see citing works
Mangiferin Improved Palmitate-Induced-Insulin Resistance by Promoting Free Fatty Acid Metabolism in HepG2 and C2C12 Cells via PPAR α : Mangiferin Improved Insulin Resistance
Zhang, Q., Kong, X., Yuan, H., Guan, H., Li, Y., & Niu, Y. (2019) · Journal of Diabetes Research · doi:10.1155/2019/2052675 · Cited by 92 · see citing works
Insulin Is a Stronger Inducer of Insulin Resistance than Hyperglycemia in Mice with Type 1 Diabetes Mellitus (T1DM)
Liu, H.-Y., Cao, S. Y., Hong, T., Han, J., Liu, Z., & Cao, W. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.016675 · Cited by 90 · see citing works
NF-κB activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions
Tantiwong, P., Shanmugasundaram, K., Monroy, A., Ghosh, S., Li, M., DeFronzo, R. A., Cersósimo, E., Sriwijitkamol, A., Mohan, S., & Musi, N. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00776.2009 · Cited by 91 · see citing works
Free Fatty Acid-Induced Hepatic Insulin Resistance is Attenuated Following Lifestyle Intervention in Obese Individuals with Impaired Glucose Tolerance
Haus, J. M., Solomon, T. P. J., Marchetti, C. M., Edmison, J. M., González, F., & Kirwan, J. P. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1101 · Cited by 90 · see citing works
Reduction of Cerebral Oxidative Stress Following Environmental Enrichment in Mice with Alzheimer‐Like Pathology
Herring, A., Blome, M., Ambrée, O., Sachser, N., Paulus, W., & Keyvani, K. (2009) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00257.x · Cited by 83 · see citing works
Protection from Palmitate-Induced Mitochondrial DNA Damage Prevents from Mitochondrial Oxidative Stress, Mitochondrial Dysfunction, Apoptosis, and Impaired Insulin Signaling in Rat L6 Skeletal Muscle Cells
Yuzefovych, L. V., Solodushko, V., Wilson, G. L., & Rachek, L. I. (2011) · Endocrinology · doi:10.1210/en.2011-1442 · Cited by 80 · see citing works
Dynamics 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 · see citing works
Skeletal Muscle Metabolic Dysfunction in Obesity and Metabolic Syndrome
Wells, G. D., Noseworthy, M. D., Hamilton, J. K., Tarnopolski, M., & Tein, I. (2008) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100007538 · Cited by 78 · see citing works
Short-term exercise training does not stimulate skeletal muscle ATP synthesis in relatives of humans with type 2 diabetes.
Kacerovsky-Bielesz, G., Chmelik, M., Ling, C., Pokan, R., Szendroedi, J., Farukuoye, M., Kacerovsky, M., Schmid, A. I., Gruber, S., Wolzt, M., et al. (2009) · Diabetes · doi:10.2337/db08-1240 · Cited by 75 · see citing works
Effects of exercise training and diet on lipid kinetics during free fatty acid-induced insulin resistance in older obese humans with impaired glucose tolerance.
Solomon, T. P. J., Haus, J., Marchetti, C. M., Stanley, W., & Kirwan, J. (2009) · American Journal of Physiology. Endocrinology and Metabolism · doi:10.1152/ajpendo.00220.2009 · Cited by 73 · see citing works

Authors: Schenk, S., & Horowitz, J. F.
Affiliations: University of Michigan (US)
Corresponding author: Horowitz, Jeffrey F.
ORCID: Schenk, Simon
Horowitz, Jeffrey F.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2007-06-01
Volume: 117
Issue: 6
Pages: 1690-1698
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci30566
PMC: PMC1866251
OpenAlex: W2102453677
Cited by: 407
References: 56
Citations by year: 2026: 4 · 2025: 9 · 2024: 9 · 2023: 17 · 2022: 11 · 2021: 15 · 2020: 24 · 2019: 18 · 2018: 19 · 2017: 20 · 2016: 20 · 2015: 23 · 2014: 24 · 2013: 32 · 2012: 37
FWCI: 11.27
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Diabetes Association
University of Michigan (M01-RR00042)
National Institutes of Health (5P60 DK20572, DK20572)
National Institute of Diabetes and Digestive and Kidney Diseases (5P60DK-20572, P60DK020572)
National Center for Research Resources (M-01RR00042, M01RR000042)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords: acute exercise, skeletal muscle insulin resistance, triglyceride synthesis, lipogenic enzymes, fatty acid metabolites, pro-inflammatory pathways, JNK activation, NF-κB, IκBα, obesity, endurance exercise, glucose disposal
MeSH terms: Adult, Fatty Acids, Female, Glycerol-3-Phosphate O-Acyltransferase, Humans, Insulin Resistance, Oxidation-Reduction, Stearoyl-CoA Desaturase, Triglycerides, Exercise, Muscle, Skeletal, Inflammation Mediators, Diacylglycerol O-Acyltransferase

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

Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid–induced insulin resistance

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks