The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
Triacylglycerol accumulation in human obesity and type 2 diabetes is associated with increased rates of skeletal muscle fatty acid transport and increased sarcolemmal FAT/CD36
Abstract
We examined whether, in human obesity and type 2 diabetes, long chain fatty acid (LCFA) transport into skeletal muscle is upregulated and contributes to an excess intramuscular triacylglycerol accumulation. In giant sarcolemmal vesicles prepared from human skeletal muscle, LCFA transport rates were upregulated ~4‐fold and were associated with an increased intramuscular triacylglycerol content in obese individuals and in type 2 diabetics. In these individuals, the increased sarcolemmal LCFA transport rate was not associated with an altered expression of FAT/CD36 or FABPpm. Instead, the increase in the LCFA transport rate was associated with an increase in sarcolemmal FAT/CD36 but not sarcolemmal FABPpm. Rates of fatty acid esterification were increased threefold in isolated human muscle strips obtained from obese subjects, while concomitantly rates of fatty acid oxidation were not altered. Thus, the increased rate of fatty acid transport may contribute to the increased rates of triacylglycerol accumulation in human skeletal muscle. The altered FAT/CD36 trafficking in muscle from obese subjects and type 2 diabetics juxtaposes the known alterations in GLUT4 trafficking, i.e., GLUT4 is known to be retained in its intracellular depots while FAT/CD36 is retained at the sarcolemma. This redistribution of FAT/CD36 to the sarcolemma may contribute to the etiology of insulin resistance in human muscle, and hence, FAT/CD36 provides another potential therapeutic target for the prevention and/or treatment of insulin resistance.
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In the citing paper
“Increased fatty acid (FA) uptake contributes to increased lipid accumulation in skeletal muscle, leading to lipotoxicity, which is known to impair muscle insulin sensitivity (2, 20).”
From Mitochondrial Fission Contributes to Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle (2012) · cites this paper as [2]
In the citing paper
“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 [96]
In the citing paper
“Thus, clinical studies have demonstrated that obese, insulin-resistant, and type 2 diabetic individuals do not exhibit a reduced capacity to oxidize fatty acids (73,74) and have normal, or even increased, mitochondrial function, as compared with lean controls (56,75).”
From Insulin sensitivity: Modulation by nutrients and inflammation (2008) · cites this paper as [73]
In the citing paper
“The importance of CD36 in FFA transport and ectopic triglyceride accumulation has been demonstrated by observations in human subjects indicating that increased skeletal muscle plasmalemma CD36 content is associated with increased muscle FFA uptake and intramyocellular triglyceride accumulation (25).”
From Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity (2009) · cites this paper as [25]
In the citing paper
“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 [25]
Citations
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Skeletal Muscle Triglyceride Levels Are Inversely Related to Insulin Action
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Skeletal muscle triglyceride levels are inversely related to insulin action
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Cited by
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Myocardial Fatty Acid Metabolism in Health and Disease
Lopaschuk, G. D., Ussher, J. R., Folmes, C. D. L., Jaswal, J. S., & Stanley, W. C. (2010) · Physiological Reviews · doi:10.1152/physrev.00015.2009 · Cited by 2,228
Steinberg, G. R., & Kemp, B. E. (2009) · Physiological Reviews · doi:10.1152/physrev.00011.2008 · Cited by 1,672
Self-citationInsulin 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
Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity
Fabbrini, E., Magkos, F., Mohammed, B. S., Pietka, T., Abumrad, N. A., Patterson, B. W., Okunade, A., & Klein, S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904944106 · Cited by 972
Scavenger receptors in homeostasis and immunity
Canton, J., Neculai, D., & Grinstein, S. (2013) · Nature Reviews Immunology · doi:10.1038/nri3515 · Cited by 838
Metadata
- Authors
- Bonen, A., Parolin, M. L., Steinberg, G. R., Calles‐Escandon, J., Tandon, N. N., Glatz, J. F. C., Luiken, J. J. F. P., Heigenhauser, G. J. F., & Dyck, D. J.
- Affiliations
- University of Guelph (CA)
- University of Waterloo (CA)
- Section of Endocrinology and Metabolism Wake Forest University School of Medicine & Baptist Medical Center Winston‐Salem North Carolina 27157
- Otsuka (United States) (US)
- Maastricht University (NL)
- McMaster University (CA)
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2004-05-07
- Volume
- 18
- Issue
- 10
- Pages
- 1144-1146
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2122852774
- Cited by
- 410
- References
- 63
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 9 · 2023: 9 · 2022: 10 · 2021: 15 · 2020: 13 · 2019: 19 · 2018: 5 · 2017: 9 · 2016: 21 · 2015: 10 · 2014: 22 · 2013: 21 · 2012: 33
- FWCI
- 14.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- triglyceride accumulation, skeletal muscle, obesity, type 2 diabetes, fatty acid uptake, FAT/CD36, FABPpm, fatty acid esterification, fatty acid oxidation, insulin resistance, GLUT4 trafficking, long-chain fatty acids
- MeSH terms
- Aged, Biological Transport, Carrier Proteins, Diabetes Mellitus, Type 2, Fatty Acids, Female, Humans, Insulin Resistance, Male, Middle Aged, Obesity, Sarcolemma, Triglycerides, Body Mass Index, Muscle, Skeletal, CD36 Antigens, Palmitic Acid, Fatty Acid-Binding Proteins
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