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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.
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“(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]
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“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]
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Metadata
- 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 (medical) › 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
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