Effects of Acute Changes of Plasma Free Fatty Acids on Intramyocellular Fat Content and Insulin Resistance in Healthy Subjects
Open accessAbstract
The reason for the 3- to 4-h delay between a rise in plasma free fatty acid (FFA) levels and the development of insulin resistance remains unknown. In the current study, we have tested the hypothesis that the delay may be caused by the need for plasma FFAs to first enter muscle cells and to be re-esterified there before causing insulin resistance. To this end, we have determined intramyocellular triglyceride (IMCL-TG) content with proton nuclear magnetic resonance (1H-NMR) spectroscopy in healthy volunteers before and 4 h after lowering of plasma FFAs (with euglycemic-hyperinsulinemic clamping) or after increasing plasma FFAs (with lipid plus heparin infusions). Increasing plasma FFAs (from 516 to 1,207 μmol/l or from 464 to 1,857 μmol/l, respectively) was associated with acute increases in IMCL-TG from 100 to 109 ± 5% (P < 0.05) or to 133 ± 11% (P < 0.01), respectively, and with a significant increase in insulin resistance (P < 0.05 after 3.5 h). Lowering of plasma FFAs from 560 to 41 μmol/l was associated with a tendency for IMCL-TG to decrease (from 100 to 95 ± 3%). Changes in plasma FFAs correlated linearly with IMCL-TG (r = 0.74, P < 0.003). The demonstration that acute changes in plasma FFAs were accompanied by corresponding changes in IMCL-TG and with the development of insulin resistance, taken together with previous reports of a close correlation between IMCL-TG and insulin resistance, supported the notion that accumulation of IMCL-TG is a step in the development of FFA-induced insulin resistance.
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
Cites
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?
Increasing plasma free fatty acid concentration in insulin-sensitive individuals increases intramyocellular fat content.
“(iii) the increase in insulin resistance caused by elevating the plasma FFA concentration in insulin sensitive individuals is associated with an increase in the intramyocellar fat content [74];”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [74]
Acute rises in circulating NEFA in healthy people cause or are linked to insulin resistance.
“Acute elevation in circulating NEFA levels in healthy individuals has been linked to insulin resistance in multiple investigations [10–13].”
From Sleep restriction increases free fatty acids in healthy men (2015) · cites this paper as [10]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Randle, P. J., Garland, P. B., Hales, C. N., & Newsholme, E. A. (1963) · The Lancet · doi:10.1016/s0140-6736(63)91500-9 · Cited by 5,093 · see citing works
Mechanisms of fatty acid-induced inhibition of glucose uptake.
Boden, G., Chen, X., Ruiz, J., White, J. V., & Rossetti, L. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117252 · Cited by 3,702 · see citing works
Self-citationThe Spread of the Obesity Epidemic in the United States, 1991-1998
Mokdad, A. H. (1999) · JAMA · doi:10.1001/jama.282.16.1519 · Cited by 2,365 · see citing works
Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM
Boden, G. (1997) · Diabetes · doi:10.2337/diab.46.1.3 · Cited by 1,728 · see citing works
Self-citationMechanism of free fatty acid-induced insulin resistance in humans.
Roden, M., Price, T. B., Perseghin, G., Petersen, K. F., Rothman, D. L., Cline, G. W., & Shulman, G. I. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118742 · Cited by 1,539 · see citing works
Griffin, M. E., Marcucci, M. J., Cline, G. W., Bell, K., Barucci, N., Lee, D., Goodyear, L. J., Kraegen, E. W., White, M. F., & Shulman, G. I. (1999) · Diabetes · doi:10.2337/diabetes.48.6.1270 · Cited by 1,267 · see citing works
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 Triglyceride Levels Are Inversely Related to Insulin Action
Pan, D. A., Lillioja, S., Kriketos, A. D., Milner, M. R., Baur, L. A., Bogardus, C., Jenkins, A. B., & Storlien, L. H. (1997) · Diabetes · doi:10.2337/diab.46.6.983 · Cited by 1,179 · see citing works
Skeletal muscle triglyceride levels are inversely related to insulin action
Pan, D. A., Lillioja, S., Kriketos, A. D., Milner, M. R., Baur, L. A., Bogardus, C., Jenkins, A. B., & Storlien, L. H. (1997) · Diabetes · doi:10.2337/diabetes.46.6.983 · Cited by 1,179 · see citing works
Methods for the assessment of human body composition: traditional and new
Lukaski, H. C. (1987) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/46.4.537 · Cited by 1,150 · see citing works
Storlien, L. H., Jenkins, A. B., Chisholm, D. J., Pascoe, W. S., Khouri, S., & Kraegen, E. W. (1991) · Diabetes · doi:10.2337/diab.40.2.280 · Cited by 967 · see citing works
Ferrannini, E., Natali, A., Bell, P., Cavallo-Perin, P., Lalic, N., & Mingrone, G. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119628 · Cited by 898 · see citing works
Borkman, M., Storlien, L. H., Pan, D. A., Jenkins, A. B., Chisholm, D. J., & Campbell, L. V. (1993) · New England Journal of Medicine · doi:10.1056/nejm199301283280404 · Cited by 835 · see citing works
Zavaroni, I., Bonora, E., Pagliara, M., Dall’Aglio, E., Luchetti, L., Buonanno, G., Bonati, P. A., Bergonzani, M., Gnudi, L., Passeri, M., et al. (1989) · New England Journal of Medicine · doi:10.1056/nejm198903163201105 · Cited by 768 · see citing works
Measurement of Plasma Glucose, Free Fatty Acid, Lactate, and Insulin for 24 h in Patients With NIDDM
Reaven, G. M., Hollenbeck, C., Jeng, C.-Y., Wu, M. S., & Chen, Y.-D. I. (1988) · Diabetes · doi:10.2337/diab.37.8.1020 · Cited by 753 · see citing works
Measurement of intracellular triglyceride stores by H spectroscopy: validation in vivo
Szczepaniak, L. S., Babcock, E. E., Schick, F., Dobbins, R. L., Garg, A., Burns, D. K., McGarry, J. D., & Stein, D. T. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.276.5.e977 · Cited by 688 · see citing works
Jacob, S., Machann, J., Rett, K., Brechtel, K., Volk, A., Renn, W., Maerker, E., Matthaei, S., Schick, F., Claussen, C. D., et al. (1999) · Diabetes · doi:10.2337/diabetes.48.5.1113 · Cited by 643 · see citing works
Effects of fat on insulin-stimulated carbohydrate metabolism in normal men.
Boden, G., Jadali, F., White, J. V., Liang, Y. T., Mozzoli, M. A., Chen, X., Coleman, E., & Smith, C. R. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115399 · Cited by 500 · see citing works
Self-citationRole of fatty acids in the pathogenesis of insulin resistance and NIDDM
Boden, G. (1997) · Diabetes · doi:10.2337/diabetes.46.1.3 · Cited by 479 · see citing works
Self-citationPrentki, M., & Corkey, B. E. (1996) · Diabetes · doi:10.2337/diab.45.3.273 · Cited by 478 · see citing works
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
Self-citationBoesch, C., Slotboom, J., Hoppeler, H. H., & Kreis, R. (1997) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910370403 · Cited by 420 · see citing works
Mechanisms of Liver and Muscle Insulin Resistance Induced by Chronic High-Fat Feeding
Oakes, N. D., Cooney, G. J., Camilleri, S., Chisholm, D. J., & Kraegen, E. W. (1997) · Diabetes · doi:10.2337/diab.46.11.1768 · Cited by 414 · see citing works
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 · see citing works
Simoneau, J., Colberg, S. R., Thaete, F. L., & Kelley, D. E. (1995) · The FASEB Journal · doi:10.1096/fasebj.9.2.7781930 · Cited by 362 · see citing works
Schick, F., Eismann, B., Jung, W., Bongers, H., Bunse, M., & Lutz, O. (1993) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910290203 · Cited by 349 · see citing works
Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes.
Boden, G., & Chen, X. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118160 · Cited by 344 · see citing works
Self-citationNMR and its Applications to Living Systems
Gadian, D. G. (1996) · doi:10.1093/oso/9780198552819.001.0001 · Cited by 289 · see citing works
Non-Esterified Fatty Acids in the Blood of Obese and Lean Subjects
GORDON, E. S. (1960) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/8.5.740 · Cited by 244 · see citing works
Dagenais, G. R., Tancredi, R. G., & Zierler, K. L. (1976) · Journal of Clinical Investigation · doi:10.1172/jci108486 · Cited by 238 · see citing works
Storlien, L. H., Jenkins, A. B., Chisholm, D. J., Pascoe, W. S., Khouri, S., & Kraegen, E. W. (1991) · Diabetes · doi:10.2337/diabetes.40.2.280 · Cited by 229 · see citing works
Koyama, K., Chen, G., Lee, Y., & Unger, R. H. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.273.4.e708 · Cited by 227 · see citing works
Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM
Reaven, G. M., Hollenbeck, C., Jeng, C. Y., et al. (1988) · Diabetes · doi:10.2337/diabetes.37.8.1020 · Cited by 183 · see citing works
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
Oakes, N. D., Bell, K. S., Furler, S. M., Camilleri, S., Saha, A. K., Ruderman, N. B., Chisholm, D. J., & Kraegen, E. W. (1997) · Diabetes · doi:10.2337/diabetes.46.12.2022 · Cited by 176 · see citing works
Effect of Hyperinsulinemia on Urea Pool Size and Substrate Oxidation Rates
Tappy, L., Owen, O. E., & Boden, G. H. (1988) · Diabetes · doi:10.2337/diab.37.9.1212 · Cited by 122 · see citing works
Self-citationMechanisms of liver and muscle insulin resistance induced by chronic high-fat feeding
Oakes, N. D., Cooney, G. J., Camilleri, S., et al. (1997) · Diabetes · doi:10.2337/diabetes.46.11.1768 · Cited by 118 · see citing works
Insulin Resistance of Muscle Glucose Transport in Rats Fed a High-Fat Diet: A Reevaluation
Han, D., Hansen, P. A., Host, H. H., & Holloszy, J. O. (1997) · Diabetes · doi:10.2337/diab.46.11.1761 · Cited by 117 · see citing works
Vock, R., Hoppeler, H. H., Claassen, H., Wu, D. X. Y., Billeter-Clark, R., Weber, J., Taylor, C. R., & Weibel, E. R. (1996) · Journal of Experimental Biology · doi:10.1242/jeb.199.8.1689 · Cited by 101 · see citing works
Effects of Therapy on the Nature and Quantity of Fuels Oxidized During Diabetic Ketoacidosis
Owen, O. E., Trapp, V. E., Reichard, G., Mozzoli, M. A., Smith, R., & Boden, G. (1980) · Diabetes · doi:10.2337/diab.29.5.365 · Cited by 51 · see citing works
Self-citationEffect of hyperinsulinemia on urea pool size and substrate oxidation rates
Tappy, L., Owen, O. E., & Boden, G. (1988) · Diabetes · doi:10.2337/diabetes.37.9.1212 · Cited by 48 · see citing works
Self-citationAcute effects of endurance exercise on mitochondrial distribution and skeletal muscle morphology
Kayar, S. R., Hoppeler, H. H., HOWALD, H., Claassen, H., & Oberholzer, F. (1986) · European Journal of Applied Physiology · doi:10.1007/bf00943344 · Cited by 46 · see citing works
Holmes, K. T., Lean, C. L., Hunt, N. H., & King, N. J. C. (1990) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910160102 · Cited by 36 · see citing works
Effects of Insulin on Fatty Acid Reesterification in Healthy Subjects
Boden, G., Chen, X.-H., Desantis, R. A., & Kendrick, Z. (1993) · Diabetes · doi:10.2337/diab.42.11.1588 · Cited by 36 · see citing works
Self-citationInsulin resistance of muscle glucose transport in rats fed a high-fat diet: a reevaluation
Han, D. H., Hansen, P. A., Host, H. H., et al. (1997) · Diabetes · doi:10.2337/diabetes.46.11.1761 · Cited by 30 · see citing works
Balschi, J. A., Hai, J. O., Wolkowicz, P. E., Straeter‐Knowlen, I. M., Evanochko, W. T., Caulfield, J., Bradley, E. L., Ku, D. D., & Pohost, G. M. (1997) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1996.9997 · Cited by 25 · see citing works
Madden, M. C., Winkle, W. B. V., Kirk, K. A., Pike, M. M., Pohost, G. M., & Wolkowicz, P. E. (1993) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(93)90203-l · Cited by 21 · see citing works
Chen, X.-H., Ruiz, J., & Boden, G. (1995) · Metabolism: Clinical and Experimental · doi:10.1016/0026-0495(95)90080-2 · Cited by 17 · see citing works
Self-citationEffects of insulin on fatty acid reesterification in healthy subjects
Boden, G., Chen, X., Desantis, R. A., et al. (1993) · Diabetes · doi:10.2337/diabetes.42.11.1588 · Cited by 10 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Simental-Mendía, L. E., Rodríguez-Moran, M., & Guerrero-Romero, F. (2008) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2008.0034 · Cited by 2,194 · see citing works
Pathophysiology of Sleep Apnea
Dempsey, J. A., Veasey, S. C., Morgan, B. J., & O'Donnell, C. P. (2010) · Physiological Reviews · doi:10.1152/physrev.00043.2008 · Cited by 2,243 · see citing works
Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes
Evans, J. L., Goldfine, I. D., Maddux, B. A., & Grodsky, G. M. (2002) · Endocrine Reviews · doi:10.1210/er.2001-0039 · Cited by 2,232 · see citing works
A comprehensive review on metabolic syndrome
Kaur, J. (2014) · Cardiology Research and Practice · doi:10.1155/2014/943162 · Cited by 1,889 · see citing works
RetractedPGC-1α, SIRT1 and AMPK, an energy sensing network that controls energy expenditure
Cantó, C., & Auwerx, J. (2009) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328328d0a4 · Cited by 1,624 · see citing works
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
Self-citationLewis, G. F., Carpentier, A. C., Adeli, K., & Giacca, A. (2002) · Endocrine Reviews · doi:10.1210/edrv.23.2.0461 · Cited by 1,328 · see citing works
Boden, G., & Shulman, G. I. (2002) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.32.s3.3.x · Cited by 1,300 · see citing works
Self-citationRole of Mitochondrial Dysfunction in Insulin Resistance
Kim, J.-A., Wei, Y., & Sowers, J. R. (2008) · Circulation Research · doi:10.1161/circresaha.107.165472 · Cited by 1,103 · see citing works
Sex differences in human adipose tissues – the biology of pear shape
Karastergiou, K., Smith, S. R., Greenberg, A. S., & Fried, S. K. (2012) · Biology of Sex Differences · doi:10.1186/2042-6410-3-13 · Cited by 1,109 · see citing works
Boden, G. H. (2008) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2008.06.007 · Cited by 852 · see citing works
Self-citationObesity, 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
Self-citationPi-Sunyer, X. (2002) · Obesity Surgery · doi:10.1007/bf03342140 · Cited by 828 · see citing works
Pathogenesis of insulin resistance in skeletal muscle
Abdul-Ghani, M. A., & DeFronzo, R. A. (2010) · Journal of Biomedicine and Biotechnology · doi:10.1155/2010/476279 · Cited by 670 · see citing works
Tripathy, D., Mohanty, P., Dhindsa, S., Syed, T., Ghanim, H., Aljada, A., & Dandona, P. (2003) · Diabetes · doi:10.2337/diabetes.52.12.2882 · Cited by 658 · see citing works
Sleep influences on obesity, insulin resistance, and risk of type 2 diabetes
Reutrakul, S., & Van Cauter, E. (2018) · Metabolism · doi:10.1016/j.metabol.2018.02.010 · Cited by 584 · see citing works
Removal of Visceral Fat Prevents Insulin Resistance and Glucose Intolerance of Aging
Gabriely, I., Ma, X. H., Yang, X. M., Atzmon, G., Rajala, M. W., Berg, A. H., Scherer, P., Rossetti, L., & Barzilai, N. (2002) · Diabetes · doi:10.2337/diabetes.51.10.2951 · Cited by 563 · see citing works
Differential Effects of Interleukin-6 and -10 on Skeletal Muscle and Liver Insulin Action In Vivo
Kim, H.-J., Higashimori, T., Park, S.-Y., Choi, H., Dong, J., Kim, Y.-J., Noh, H.-L., Cho, Y.-R., Cline, G., Kim, Y.-B., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.4.1060 · Cited by 534 · see citing works
The Subtle Balance between Lipolysis and Lipogenesis: A Critical Point in Metabolic Homeostasis
Saponaro, C., Gaggini, M., Carli, F., & Gastaldelli, A. (2015) · Nutrients · doi:10.3390/nu7115475 · Cited by 531 · see citing works
Lipid accumulation in non-adipose tissue and lipotoxicity
van Herpen, N. A., & Schrauwen-Hinderling, V. B. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.11.049 · Cited by 500 · see citing works
Skeletal Muscle Lipid Metabolism in Exercise and Insulin Resistance
Kiens, B. (2006) · Physiological Reviews · doi:10.1152/physrev.00023.2004 · Cited by 478 · see citing works
Insulin resistance in chronic kidney disease: a systematic review
Spoto, B., Pisano, A., & Zoccali, C. (2016) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00340.2016 · Cited by 453 · see citing works
Schenk, S., & Horowitz, J. F. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30566 · Cited by 407 · see citing works
Dose-Response Effect of Elevated Plasma Free Fatty Acid on Insulin Signaling
Belfort, R., Mandarino, L., Kashyap, S., Wirfel, K., Pratipanawatr, T., Berria, R., DeFronzo, R. A., & Cusi, K. (2005) · Diabetes · doi:10.2337/diabetes.54.6.1640 · Cited by 404 · see citing works
M <scp>USCLE</scp> T <scp>RIGLYCERIDE AND</scp> I <scp>NSULIN</scp> R <scp>ESISTANCE</scp>
Kelley, D. E., Goodpaster, B. H., & Storlien, L. (2002) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.22.010402.102912 · Cited by 364 · see citing works
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
Dietary phytochemicals and their potential effects on obesity: A review
González-Castejón, M., & Rodríguez‐Casado, A. (2011) · Pharmacological Research · doi:10.1016/j.phrs.2011.07.004 · Cited by 375 · 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
Bruce, C. R., Carey, A. L., Hawley, J. A., & Febbraio, M. A. (2003) · Diabetes · doi:10.2337/diabetes.52.9.2338 · Cited by 318 · see citing works
McHill, A. W., & Wright, K. P. (2017) · Obesity Reviews · doi:10.1111/obr.12503 · Cited by 316 · see citing works
Link between obesity and type 2 diabetes
Golay, A., & Ybarra, J. (2005) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2005.07.010 · Cited by 301 · see citing works
Yuzefovych, L. V., Musiyenko, S. I., Wilson, G. L., & Rachek, L. I. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054059 · Cited by 302 · see citing works
Skeletal muscle fat oxidation: Timing and flexibility are everything
Kelley, D. E. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25758 · Cited by 298 · see citing works
Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1
Chen, H. C., Smith, S. J., Ladha, Z., Jensen, D. R., Ferreira, L. D., Pulawa, L. K., McGuire, J. G., Pitas, R. E., Eckel, R. H., & Farese, R. V. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14672 · Cited by 329 · see citing works
Gastaldelli, A., Harrison, S. A., Belfort-Aguilar, R., Hardies, L. J., Balas, B., Schenker, S., & Cusi, K. (2009) · Hepatology · doi:10.1002/hep.23116 · Cited by 285 · see citing works
The links between sleep duration, obesity and type 2 diabetes mellitus
Antza, C., Kostopoulos, G., Mostafa, S., Nirantharakumar, K., & Tahrani, A. (2021) · Journal of Endocrinology · doi:10.1530/joe-21-0155 · Cited by 294 · see citing works
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
Fatty acid—induced inflammation and insulin resistance in skeletal muscle and liver
Boden, G. (2006) · Current Diabetes Reports · doi:10.1007/s11892-006-0031-x · Cited by 276 · see citing works
Self-citationHajri, T., Han, X. X., Bonen, A., & Abumrad, N. A. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14596 · Cited by 277 · see citing works
Intramuscular and Liver Triglycerides Are Increased in the Elderly
Cree‐Green, M., Newcomer, B. R., Katsanos, C. S., Sheffield‐Moore, M., Chinkes, D. L., Aarsland, A. A., Urban, R. J., & Wolfe, R. R. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031986 · Cited by 273 · see citing works
Peroxynitrite and Vascular Endothelial Dysfunction in Diabetes Mellitus
Zou, M., Cohen, R. A., & Ullrich, V. (2004) · Endothelium · doi:10.1080/10623320490482619 · Cited by 270 · see citing works
Mitochondrial dysfunction and lipotoxicity
Schrauwen, P., Schrauwen-Hinderling, V., Hoeks, J., & Hesselink, M. K. C. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.09.011 · Cited by 268 · see citing works
Stanhope, K. L., & Havel, P. J. (2008) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3282f2b24a · Cited by 272 · see citing works
Robertson, M. D., Currie, J. M., Morgan, L., Jewell, D. P., & Frayn, K. N. (2003) · Diabetologia · doi:10.1007/s00125-003-1081-0 · Cited by 263 · see citing works
Effect of intermittent fasting and refeeding on insulin action in healthy men
Halberg, N., Henriksen, M., Söderhamn, N., Stallknecht, B., Ploug, T., Schjerling, P., & Dela, F. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00683.2005 · Cited by 259 · see citing works
The role of intramuscular lipid in insulin resistance
Hegarty, B. D., Furler, S. M., Ye, J.-M., Cooney, G. J., & Kraegen, E. W. (2003) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.2003.01162.x · Cited by 256 · see citing works
Yin, B., Wu, Z., Xia, Y., Xiao, S., Chen, L., & Li, Y. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-01886-5 · Cited by 248 · see citing works
Insulin Resistance: Metabolic Mechanisms and Consequences in the Heart
Abel, E. D., O’Shea, K. M., & Ramasamy, R. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.241984 · Cited by 244 · see citing works
Pathogenesis of Lipid Disorders in Insulin Resistance: a Brief Review
Bjornstad, P., & Eckel, R. H. (2018) · Current Diabetes Reports · doi:10.1007/s11892-018-1101-6 · Cited by 245 · see citing works
Regulation of HSL serine phosphorylation in skeletal muscle and adipose tissue
Watt, M. J., Holmes, A. G., Pinnamaneni, S. K., GARNHAM, A. P., Steinberg, G. R., Kemp, B. E., & Febbraio, M. A. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00361.2005 · Cited by 241 · see citing works
van 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
Mohamed, G. A., Ibrahim, S. R. M., Elkhayat, E. S., & Dine, R. S. E. (2014) · Bulletin of Faculty of Pharmacy Cairo University · doi:10.1016/j.bfopcu.2014.05.001 · Cited by 238 · see citing works
van Loon, L. J. C., Koopman, R., Stegen, J. H. C. H., Wagenmakers, A. J. M., KEIZER, H. A., & Saris, W. H. M. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.052431 · Cited by 231 · see citing works
Hajri, T., Han, X. X., Bonen, A., & Abumrad, N. A. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0214596 · Cited by 228 · see citing works
Thamer, C., Machann, J., Bachmann, O. P., Haap, M. M., Dahl, D. B., Wietek, B., Tschritter, O., Niess, A. M., Brechtel, K., Fritsche, A., et al. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021674 · Cited by 228 · see citing works
Increased lipid availability impairs insulin-stimulated ATP synthesis in human skeletal muscle
Brehm, A., Krssak, M., Schmid, A. I., Nowotny, P., Waldhäusl, W., & Roden, M. (2006) · Diabetes · doi:10.2337/diabetes.55.01.06.db05-1286 · Cited by 239 · see citing works
AMP‐activated protein kinase: role in metabolism and therapeutic implications
Schimmack, G., DeFronzo, R. A., & Musi, N. (2006) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2005.00561.x · Cited by 229 · see citing works
Kim, J. K., Gimeno, R. E., Higashimori, T., Kim, H., Choi, H., Punreddy, S., Mozell, R. L., Tan, G., Stricker‐Krongrad, A., Hirsch, D. J., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci18917 · Cited by 244 · see citing works
Metabolic, Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption
Romano, K. A., Martinez-del Campo, A., Kasahara, K., Chittim, C. L., Vivas, E. I., Amador-Noguez, D., Balskus, E. P., & Rey, F. E. (2017) · Cell Host & Microbe · doi:10.1016/j.chom.2017.07.021 · Cited by 224 · see citing works
Interaction between free fatty acids and glucose metabolism
Boden, G. H. (2002) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200209000-00014 · Cited by 222 · see citing works
Self-citationSinha, S., Perdomo, G., Brown, N. F., & O'Doherty, R. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406514200 · Cited by 215 · see citing works
Roles of Leptin and Ghrelin in the Loss of Body Weight Caused by a Low Fat, High Carbohydrate Diet
Weigle, D. S., Cummings, D. E., Newby, P. D., Breen, P. A., Frayo, R. S., Matthys, C. C., Callahan, H. S., & Purnell, J. Q. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021262 · Cited by 212 · see citing works
Kim, J. K., Gimeno, R. E., Higashimori, T., Kim, H., Choi, H., Punreddy, S., Mozell, R. L., Tan, G., Stricker‐Krongrad, A., Hirsch, D. J., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200418917 · Cited by 212 · see citing works
Jacobsen, S., Brøns, C., Bork-Jensen, J., Ribel-Madsen, R., Yang, B., Lara, E., Hall, E., Calvanese, V., Nilsson, E., Jørgensen, S. W., et al. (2012) · Diabetologia · doi:10.1007/s00125-012-2717-8 · Cited by 197 · see citing works
Després, J.-P. (2006) · European Heart Journal Supplements · doi:10.1093/eurheartj/sul002 · Cited by 205 · see citing works
Skeletal muscle lipid accumulation in obesity, insulin resistance, and type 2 diabetes
Goodpaster, B. H., & Wolf, D. L. (2004) · Pediatric Diabetes · doi:10.1111/j.1399-543x.2004.00071.x · Cited by 206 · see citing works
Role of proton MR for the study of muscle lipid metabolism
Boesch, C., Machann, J., Vermathen, P., & Schick, F. (2006) · NMR in Biomedicine · doi:10.1002/nbm.1096 · Cited by 204 · see citing works
Use of intramuscular triacylglycerol as a substrate source during exercise in humans
van Loon, L. J. C. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00368.2004 · Cited by 205 · see citing works
Intramyocellular Lipid Content in Human Skeletal Muscle
Schrauwen‐Hinderling, V. B., Hesselink, M. K. C., Schrauwen, P., & Kooi, M. E. (2006) · Obesity · doi:10.1038/oby.2006.47 · Cited by 202 · see citing works
Emerging Role of Nitric Oxide and Heat Shock Proteins in Insulin Resistance
Molina, M. N., Ferder, L., & Manucha, W. A. (2015) · Current Hypertension Reports · doi:10.1007/s11906-015-0615-4 · Cited by 200 · see citing works
Pathogenesis and pathophysiology of the cardiometabolic syndrome
Kirk, E. P., & Klein, S. (2009) · The Journal of Clinical Hypertension · doi:10.1111/j.1559-4572.2009.00054.x · Cited by 195 · see citing works
Kim, H., Haluzı́k, M., Shyr, Z. A., Yau, D., Joseph, J. W., Fernandez, A. M., Reitman, M. L., Yakar, S., STANNARD, B. S., Héron‐Milhavet, L., et al. (2003) · Diabetes · doi:10.2337/diabetes.52.7.1770 · Cited by 189 · see citing works
Rasmussen, B. B., Holmbäck, U. C., Volpi, E., Morio, B., Paddon‐Jones, D., & Wolfe, R. R. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15715 · Cited by 223 · see citing works
Endurance Training and Obesity
Venables, M., & Jeukendrup, A. E. (2008) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e31815f256f · Cited by 189 · see citing works
Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor
Tenenbaum, A., Klempfner, R., & Fisman, E. Z. (2014) · Cardiovascular Diabetology · doi:10.1186/s12933-014-0159-y · Cited by 188 · see citing works
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 · 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
PPARγ regulates adipocyte cholesterol metabolism via oxidized LDL receptor 1
Chui, P. C., Guan, H.-P., Lehrke, M., & Lazar, M. A. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24130 · Cited by 178 · see citing works
Mitochondrial Dysfunction Plays Central Role in Nonalcoholic Fatty Liver Disease
Ramanathan, R., Ali, A. H., & Ibdah, J. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137280 · Cited by 179 · see citing works
Intramyocellular lipids and insulin resistance
Machann, J., Häring, H. U., Schick, F., & Stümvoll, M. (2004) · Diabetes Obesity and Metabolism · doi:10.1111/j.1462-8902.2004.00339.x · Cited by 172 · see citing works
Dose-dependent effects of testosterone on regional adipose tissue distribution in healthy young men.
Woodhouse, L., Gupta, N., Bhasin, M., Singh, A. B., Ross, R., Phillips, J., & Bhasin, S. (2004) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2003-031492 · Cited by 159 · see citing works
Qian, J., Dalla Man, C., Morris, C. J., Cobelli, C., & Scheer, F. A. J. L. (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13391 · Cited by 170 · see citing works
PATHOGENESIS OF TYPE 2 DIABETES
Boden, G. H. (2001) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(05)70216-4 · Cited by 170 · see citing works
Self-citationAnderwald, C. H., Bernroider, E., Krššák, M., Stingl, H., Brehm, A., Bischof, M. G., Nowotny, P., Roden, M., & Waldhäusl, W. K. (2002) · Diabetes · doi:10.2337/diabetes.51.10.3025 · Cited by 168 · see citing works
Nontraditional Risk Factors for Cardiovascular Disease in Diabetes
Fonseca, V. A., Desouza, C. V., Asnani, S., & Jialal, I. (2004) · Endocrine Reviews · doi:10.1210/er.2002-0034 · Cited by 165 · see citing works
Dasgupta, S., Bhattacharya, S., Biswas, A., Majumdar, S. S., Mukhopadhyay, S., Ray, S., & Bhattacharya, S. (2010) · Biochemical Journal · doi:10.1042/bj20100330 · Cited by 168 · see citing works
Lipids and Glucose in Type 2 Diabetes
Boden, G. H., & Laakso, M. (2004) · Diabetes Care · doi:10.2337/diacare.27.9.2253 · Cited by 168 · see citing works
Self-citationHofmann, S. M., Zhou, L., Pérez–Tilve, D., Greer, T., Grant, E., Wancata, L., Thomas, A., Pfluger, P. T., Basford, J. E., Gilham, D., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31929 · Cited by 166 · see citing works
Food Polyphenols and Type II Diabetes Mellitus: Pharmacology and Mechanisms
Naz, R., Saqib, F., Awadallah, S. M., Wahid, M., Latif, M. F., Iqbal, I., & Mubarak, M. S. (2023) · Molecules · doi:10.3390/molecules28103996 · Cited by 175 · see citing works
Intracellular Lipid Accumulation in Liver and Muscle and the Insulin Resistance Syndrome
Lara‐Castro, C., & Garvey, W. T. (2008) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2008.09.002 · Cited by 163 · 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
Effect of the dietary fat quality on insulin sensitivity
Galgani, J. E., Uauy, R. D., Aguirre, C. A., & Díaz, E. O. (2008) · British Journal of Nutrition · doi:10.1017/s0007114508894408 · Cited by 154 · see citing works
Browning, J. D., Baxter, J., Satapati, S., & Burgess, S. C. (2012) · Journal of Lipid Research · doi:10.1194/jlr.p020867 · Cited by 160 · see citing works
Pediatric obesity phenotyping by magnetic resonance methods.
Shen, W., Liu, H., Punyanitya, M., Chen, J., & Heymsfield, S. B. (2005) · PubMed · Cited by 159 · see citing works
Machann, J., Thamer, C., Schnödt, B., Stefan, N., Stümvoll, M., Häring, H.-U., Claussen, C. D., Schick, F., & Fritsche, A. (2005) · Magnetic Resonance Materials in Physics Biology and Medicine · doi:10.1007/s10334-005-0104-x · Cited by 157 · see citing works
Watt, M. J., Heigenhauser, G. J. F., & Spriet, L. L. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00197.2002 · Cited by 156 · see citing works
Sleep restriction increases free fatty acids in healthy men
Broussard, J. L., Chapotot, F., Abraham, V., Day, A., Delebecque, F., Whitmore, H. R., & Tasali, E. (2015) · Diabetologia · doi:10.1007/s00125-015-3500-4 · Cited by 156 · 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
Plasma Free Fatty Acid Concentration as a Modifiable Risk Factor for Metabolic Disease
Henderson, G. C. (2021) · Nutrients · doi:10.3390/nu13082590 · Cited by 152 · see citing works
Kautzky-Willer, A., Krssak, M., Winzer, C., Pacini, G., Tura, A., Farhan, S., Wagner, O., Brabant, G., Horn, R., Stingl, H., et al. (2003) · Diabetes · doi:10.2337/diabetes.52.2.244 · Cited by 150 · see citing works
- Authors
- Boden, G., Lebed, B., Schatz, M., Homko, C., & Lemieux, S.
- Affiliations
- Division of Endocrinology/Diabetes/Metabolism, the General Clinical Research Center, and the
- Temple University (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2001-07-01
- Volume
- 50
- Issue
- 7
- Pages
- 1612-1617
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2112375566
- Cited by
- 597
- References
- 41
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 11 · 2023: 21 · 2022: 13 · 2021: 27 · 2020: 16 · 2019: 20 · 2018: 15 · 2017: 13 · 2016: 18 · 2015: 20 · 2014: 23 · 2013: 16 · 2012: 29
- FWCI
- 27.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag007988-10, 5r01aa010221-03)
- National Institute on Alcohol Abuse and Alcoholism (R01-AA-10221)
- National Institute on Aging (R01-AG07988)
- National Center for Research Resources (RR-349)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- plasma free fatty acids, intramyocellular triglyceride, insulin resistance, fatty acid re-esterification, lipid infusion, heparin, healthy volunteers
- MeSH terms
- Adipose Tissue, Adult, Blood Glucose, Body Composition, Calorimetry, Indirect, Fatty Acids, Nonesterified, Female, Humans, Insulin, Insulin Resistance, Male, Muscles, Magnetic Resonance Spectroscopy, Oxidation-Reduction, Reference Values, Triglycerides
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
