Cited by 597Diabetes, Cardiovascular Risks, and LipoproteinsAdipose Tissue and MetabolismLipid metabolism and biosynthesis

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Effects of Acute Changes of Plasma Free Fatty Acids on Intramyocellular Fat Content and Insulin Resistance in Healthy Subjects

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Boden, Guenther, Lebed, Brett, Schatz, Melanie, Homko, Carol, Lemieux, Susan·2001·Diabetes

DOI 10.2337/diabetes.50.7.1612

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Abstract

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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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
DOI: 10.2337/diabetes.50.7.1612
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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Effects of Acute Changes of Plasma Free Fatty Acids on Intramyocellular Fat Content and Insulin Resistance in Healthy Subjects

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