Lipid-Induced Insulin Resistance Is Associated With an Impaired Skeletal Muscle Protein Synthetic Response to Amino Acid Ingestion in Healthy Young Men
Open accessAbstract
The ability to maintain skeletal muscle mass appears to be impaired in insulin-resistant conditions, such as type 2 diabetes, that are characterized by muscle lipid accumulation. The current study investigated the effect of acutely increasing lipid availability on muscle protein synthesis. Seven healthy young male volunteers underwent a 7-h intravenous infusion of l-[ring-2H5]phenylalanine on two randomized occasions combined with 0.9% saline or 10% Intralipid at 100 mL/h. After a 4-h “basal” period, a 21-g bolus of amino acids was administered and a 3-h hyperinsulinemic-euglycemic clamp was commenced (“fed” period). Muscle biopsy specimens were obtained from the vastus lateralis at 1.5, 4, and 7 h. Lipid infusion reduced fed whole-body glucose disposal by 20%. Furthermore, whereas the mixed muscle fractional synthetic rate increased from the basal to the fed period during saline infusion by 2.2-fold, no change occurred during lipid infusion, despite similar circulating insulin and leucine concentrations. This “anabolic resistance” to insulin and amino acids with lipid infusion was associated with a complete suppression of muscle 4E-BP1 phosphorylation. We propose that increased muscle lipid availability may contribute to anabolic resistance in insulin-resistant conditions by impairing translation initiation.
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- Authors
- Stephens, F. B., Chee, C., Wall, B. T., Murton, A. J., Shannon, C. E., van Loon, L. J. C., & Tsintzas, K.
- Affiliations
- University of Nottingham (GB)
- Maastricht University (NL)
- School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands
- Corresponding author
- Stephens, Francis B.
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2014-12-18
- Volume
- 64
- Issue
- 5
- Pages
- 1615-1620
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2161782364
- Cited by
- 102
- References
- 25
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 11 · 2020: 10 · 2019: 11 · 2018: 15 · 2017: 7 · 2016: 18 · 2015: 5
- FWCI
- 4.95
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Open Research Exeter (University of Exeter) (acceptedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Research Bank (Australian Catholic University) (submittedVersion)
- Nottingham ePrints (University of Nottingham) (submittedVersion, cc-by)
- Figshare (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- British Nutrition Foundation
- Universiteit Maastricht
- Medical Research Council (MR/K00414X/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- insulin resistance, skeletal muscle protein synthesis, muscle lipid accumulation, Intralipid infusion, amino acid ingestion, hyperinsulinemic-euglycemic clamp, 4E-BP1 phosphorylation, translation initiation, anabolic resistance, type 2 diabetes, muscle mass preservation, glucose disposal
- MeSH terms
- Amino Acids, Emulsions, Gene Expression Regulation, Glucose, Humans, Insulin Resistance, Male, Muscle Proteins, Phospholipids, Soybean Oil, Signal Transduction, Muscle, Skeletal, Young Adult
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