Increased Rates of Fatty Acid Uptake and Plasmalemmal Fatty Acid Transporters in Obese Zucker Rats
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Giant vesicles were used to study the rates of uptake of long-chain fatty acids by heart, skeletal muscle, and adipose tissue of obese and lean Zucker rats. With obesity there was an increase in vesicular fatty acid uptake of 1.8-fold in heart, muscle and adipose tissue. In some tissues only fatty acid translocase (FAT) mRNA (heart, +37%; adipose, +80%) and fatty acid-binding protein (FABPpm) mRNA (heart, +148%; adipose, +196%) were increased. At the protein level FABPpm expression was not changed in any tissues except muscle (+14%), and FAT/CD36 protein content was altered slightly in adipose tissue (+26%). In marked contrast, the plasma membrane FAT/CD36 protein was increased in heart (+60%), muscle (+80%), and adipose tissue (+50%). The plasma membrane FABPpm was altered only in heart (+50%) and adipose tissues (+70%). Thus, in obesity, alterations in fatty acid transport in metabolically important tissues are not associated with changes in fatty acid transporter mRNAs or altered fatty acid transport protein expression but with their increased abundance at the plasma membrane. We speculate that in obesity fatty acid transporters are relocated from an intracellular pool to the plasma membrane in heart, muscle, and adipose tissues.
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CD36 has an important role in long-chain fatty acid uptake into skeletal muscle in rodents and humans, and its concentration and activity increase after exercise.
“There is abundant evidence which indicates that CD36 plays an important role in LCFA uptake into skeletal muscle in rodents and human and its concentration and activity are increased following exercise [89–96].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [92]
Increased plasmalemma skeletal muscle CD36 is associated with increased FFA uptake and insulin resistance in animal models and obese and diabetic human subjects.
“The potential importance of CD36 in regulating insulin sensitivity is supported by studies conducted in animal models and in obese and diabetic human subjects that found increased plasmalemma skeletal muscle CD36 was associated with increased FFA uptake and insulin resistance (25,30,31)”
From Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity (2009) · cites this paper as [30]
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Kiens, B., Roepstorff, C., Glatz, J. F. C., Bonen, A., Schjerling, P., Knudsen, J., & Nielsen, J. N. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01278.2003 · Cited by 143 · see citing works
Self-citationPhysical inactivity and obesity: links with insulin resistance and type 2 diabetes mellitus
Venables, M. C., & Jeukendrup, A. E. (2009) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.983 · Cited by 137 · see citing works
Bonen, A., Tandon, N. N., Glatz, J. F. C., Luiken, J. J. F. P., & Heigenhauser, G. J. F. (2006) · International Journal of Obesity · doi:10.1038/sj.ijo.0803212 · Cited by 138 · see citing works
Self-citationDyck, D. J. (2009) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h09-037 · Cited by 136 · see citing works
Self-citationCardiac fatty acid oxidation in heart failure associated with obesity and diabetes
Fukushima, A., & Lopaschuk, G. D. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.03.020 · Cited by 139 · see citing works
Bonen, A., Han, X., Habets, D. D. J., Febbraio, M., Glatz, J. F. C., & Luiken, J. J. F. P. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00579.2006 · Cited by 134 · see citing works
Self-citationRegular exercise is associated with a protective metabolic phenotype in the rat heart
Burelle, Y., Wambolt, R. B., Grist, M., Parsons, H. L., Chow, J. C. F., Antler, C., Bonen, A., Keller, A., Dunaway, G., Popov, K. M., et al. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00925.2003 · Cited by 129 · see citing works
Self-citationSmith, A. C., Mullen, K. L., Junkin, K. A., Nickerson, J., Chabowski, A., Bonen, A., & Dyck, D. J. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00677.2006 · Cited by 127 · see citing works
Self-citationSchwenk, R. W., Dirkx, E., Coumans, W. A., Bonen, A., Klip, A., Glatz, J. F. C., & Luiken, J. J. F. P. (2010) · Diabetologia · doi:10.1007/s00125-010-1832-7 · Cited by 126 · see citing works
Self-citationMetabolic dysfunction in diabetic cardiomyopathy
Isfort, M. C., Stevens, S. C. W., Schaffer, S. W., Jong, C. J., & Wold, L. E. (2013) · Heart Failure Reviews · doi:10.1007/s10741-013-9377-8 · Cited by 126 · see citing works
Changes in fatty acid transport and transporters are related to the severity of insulin deficiency
Luiken, J. J. F. P., Arumugam, Y., Bell, R. C., Calles-Escandón, J., Tandon, N. N., Glatz, J. F. C., & Bonen, A. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00011.2002 · Cited by 126 · see citing works
Self-citationRegulation of skeletal muscle fat oxidation during exercise in humans
SPRIET, L. L. (2002) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-200209000-00013 · Cited by 126 · see citing works
CD36 as a gatekeeper of myocardial lipid metabolism and therapeutic target for metabolic disease
Glatz, J. F. C., Heather, L. C., & Luiken, J. J. F. P. (2023) · Physiological Reviews · doi:10.1152/physrev.00011.2023 · Cited by 130 · see citing works
Self-citationBrinkmann, J. F. F., Abumrad, N. A., Ibrahimi, A., Vandervusse, G. J., & Glatz, J. F. C. (2002) · Biochemical Journal · doi:10.1042/bj20020747 · Cited by 124 · see citing works
Self-citationNahlé, Z., Hsieh, M., Pietka, T., Coburn, C. T., Grimaldi, P. A., Zhang, M. Q., Das, D., & Abumrad, N. A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m706478200 · Cited by 122 · see citing works
van den Brom, C. E., Huisman, M. C., Vlasblom, R., Boontje, N. M., Duijst, S., Lubberink, M., Molthoff, C. F. M., Lammertsma, A. A., van der Velden, J., Boer, C., et al. (2009) · Cardiovascular Diabetology · doi:10.1186/1475-2840-8-39 · Cited by 122 · see citing works
Contribution of FAT/CD36 to the regulation of skeletal muscle fatty acid oxidation: an overview
Holloway, G. P., Luiken, J. J. F. P., Glatz, J. F. C., Spriet, L. L., & Bonen, A. (2008) · Acta Physiologica · doi:10.1111/j.1748-1716.2008.01878.x · Cited by 120 · see citing works
Self-citationWang, P., Lloyd, S. G., Zeng, H., Bonen, A., & Chatham, J. C. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00935.2004 · Cited by 118 · see citing works
Self-citationZhou, X., Ma, L., Habibi, J., Whaley-Connell, A., Hayden, M. R., Tilmon, R. D., Brown, A. N., Kim, J.-A., DeMarco, V. G., & Sowers, J. R. (2010) · Hypertension · doi:10.1161/hypertensionaha.109.145136 · Cited by 116 · see citing works
He, J.-H., Lee, J.-H., Febbraio, M., & Xie, W. (2011) · Experimental biology and medicine · doi:10.1258/ebm.2011.011128 · Cited by 122 · see citing works
Lipid metabolism in hepatic steatosis
Bradbury, M. W., & Berk, P. D. (2004) · Clinics in Liver Disease · doi:10.1016/j.cld.2004.04.005 · Cited by 115 · see citing works
Chabowski, A., Coort, S. L., Calles-Escandón, J., Tandon, N. N., Glatz, J. F. C., Luiken, J. J. F. P., & Bonen, A. (2005) · FEBS Letters · doi:10.1016/j.febslet.2004.11.118 · Cited by 112 · see citing works
Self-citationInsulin stimulates fatty acid transport by regulating expression of FAT/CD36 but not FABPpm
Chabowski, A., Coort, S. L., Calles-Escandón, J., Tandon, N. N., Glatz, J. F. C., Luiken, J. J. F. P., & Bonen, A. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00573.2003 · Cited by 110 · see citing works
Self-citationAtkinson, L. L., Kozak, R., Kelly, S. E., Onay-Beşi̇kçi̇, A., Russell, J. C., & Lopaschuk, G. D. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00360.2002 · Cited by 110 · see citing works
Holloway, G. P., Benton, C. R., Mullen, K. L., Yoshida, Y., Snook, L. A., Han, X.-X., Glatz, J. F. C., Luiken, J. J. F. P., Lally, J., Dyck, D. J., et al. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90896.2008 · Cited by 107 · see citing works
Self-citationChabowski, A., Górski, J., Luiken, J. J. F. P., Glatz, J. F. C., & Bonen, A. (2007) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2007.10.017 · Cited by 106 · see citing works
Self-citationImpaired skeletal muscle substrate oxidation in glucose-intolerant men improves after weight loss
Corpeleijn, E., Mensink, M., Kooi, M. E., Roekaerts, P. M. H. J., Saris, W. H. M., & Blaak, E. E. (2008) · Obesity · doi:10.1038/oby.2008.24 · Cited by 104 · see citing works
Sheedfar, F., Sung, M. M. Y., Aparicio-Vergara, M., Kloosterhuis, N., Miquilena-Colina, M. E., Vargas‐Castrillón, J., Febbraio, M., Jacobs, R. L., de Bruin, A., Vinciguerra, M., et al. (2014) · Aging · doi:10.18632/aging.100652 · Cited by 102 · see citing works
Clarke, D. C., Miskovic, D., Han, X.-X., Calles-Escandón, J., Glatz, J. F. C., Luiken, J. J. F. P., Heikkila, J. J., & Bonen, A. (2004) · Physiological Genomics · doi:10.1152/physiolgenomics.00190.2003 · Cited by 100 · see citing works
Self-citationMolecular mechanisms of cardiac pathology in diabetes – Experimental insights
Varma, U., Koutsifeli, P., Benson, V. L., Mellor, K. M., & Delbridge, L. M. D. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.10.035 · Cited by 99 · see citing works
Coort, S. L., Bonen, A., Vusse, G. J., Glatz, J. F. C., & Luiken, J. J. F. P. (2006) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-005-9030-5 · Cited by 99 · see citing works
Self-citationFukushima, A., & Lopaschuk, G. D. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.07.020 · Cited by 94 · see citing works
Alterations in energy metabolism in cardiomyopathies
Taha, M., & Lopaschuk, G. D. (2007) · Annals of Medicine · doi:10.1080/07853890701618305 · Cited by 91 · see citing works
Steinberg, G. R., Dyck, D. J., Calles-Escandon, J., Tandon, N. N., Luiken, J. J. F. P., Glatz, J. F. C., & Bonen, A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m107683200 · Cited by 91 · see citing works
Self-citationBenton, C. R., Wright, D. C., & Bonen, A. (2008) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h08-074 · Cited by 91 · see citing works
Self-citationD'souza, A. M., Beaudry, J. L., Szigiato, A.-A., Trumble, S. J., Snook, L. A., Bonen, A., Giacca, A., & Riddell, M. C. (2012) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00378.2011 · Cited by 89 · see citing works
Self-citationThe role of CD36 in the regulation of myocardial lipid metabolism
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Regulation of fatty acid transport and membrane transporters in health and disease
Bonen, A., Luiken, J. J. F. P., & Glatz, J. F. C. (2002) · Springer eBooks · doi:10.1007/978-1-4419-9270-3_23 · Cited by 88 · see citing works
Self-citationPuchałowicz, K., & Rać, M. E. (2020) · Cells · doi:10.3390/cells9081877 · Cited by 84 · see citing works
Bell, J. A., Reed, M. A., Consitt, L. A., Martin, O. J., Haynie, K. R., Hulver, M. W., Muoio, D. M., & Dohm, G. L. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1596 · Cited by 87 · see citing works
Basic disturbances in skeletal muscle fatty acid metabolism in obesity and type 2 diabetes mellitus
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The Crucial Role of C18-Cer in Fat-Induced Skeletal Muscle Insulin Resistance
Błachnio-Zabielska, A. U., Chacińska, M., Vendelbo, M. H., & Zabielski, P. (2016) · Cellular Physiology and Biochemistry · doi:10.1159/000453174 · Cited by 81 · see citing works
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Self-citationMyocardial substrate metabolism in obesity
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Lipid metabolism, exercise and insulin action
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- Authors
- Luiken, J. J. F. P., Arumugam, Y., Dyck, D. J., Bell, R. C., Pelsers, M. M. L., Turcotte, L. P., Tandon, N. N., Glatz, J. F. C., & Bonen, A.
- Affiliations
- University of Waterloo (CA)
- University of Guelph (CA)
- University of Alberta (CA)
- University of Southern California (US)
- Maastricht University (NL)
- Corresponding author
- Bonen, Arend
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-11
- Volume
- 276
- Issue
- 44
- Pages
- 40567-40573
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2069262764
- Cited by
- 282
- References
- 42
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 17 · 2020: 10 · 2019: 5 · 2018: 6 · 2017: 6 · 2016: 10 · 2015: 5 · 2014: 7 · 2013: 14 · 2012: 14
- FWCI
- 8.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29ar045168-04)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 45168)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- fatty acid uptake, obesity, Zucker rats, fatty acid translocase, FAT/CD36, fatty acid binding protein, plasma membrane localization, heart, skeletal muscle, adipose tissue, vesicular uptake
- MeSH terms
- Animals, Fatty Acids, Female, Kinetics, Membrane Glycoproteins, Obesity, Rats, Zucker, RNA, Messenger, CD36 Antigens, Organic Anion Transporters, Rats
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