The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid–induced insulin resistance
Open accessAbstract
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.
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“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]
Experimental — accuracy not yet measuredIn the citing paper
“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]
In the citing paper
“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 the citing paper
“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]
In the citing paper
“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]
In the citing paper
“In man, a single bout of exercise was sufficient to induce similar changes, in which increased DGAT1 expression in muscle was associated with increased concentrations of triglyceride, reduced concentrations of diacylglycerol, and improved insulin sensitivity.64”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [64]
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1 retracted
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A central role for JNK in obesity and insulin resistance
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Cited by
Sorted by citations
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
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
Exercise Metabolism and the Molecular Regulation of Skeletal Muscle Adaptation
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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
“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].”
BackgroundLipid 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 1,701
Metadata
- Authors
- Schenk, S., & Horowitz, J. F.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Horowitz, Jeffrey F.
- Venue
- Journal of Clinical Investigation
- Published
- 2007-06-01
- Volume
- 117
- Issue
- 6
- Pages
- 1690-1698
- ISSN
- 0021-9738 (ISSN-L)
- 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 (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › 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
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