Lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men

Stephens, Francis B.; Chee, Carolyn; Wall, Benjamin T.; Murton, Andrew J.; Shannon, Chris E.; van Loon, Luc J.C.; Tsintzas, Kostas

Abstract

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.

Citation

Stephens, F. B., Chee, C., Wall, B. T., Murton, A. J., Shannon, C. E., van Loon, L. J., & Tsintzas, K. (2015). Lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men. Diabetes, 64(5), https://doi.org/10.2337/db14-0961

• Journal Article Type: Article
• Acceptance Date: Dec 11, 2014
• Online Publication Date: Apr 23, 2015
• Publication Date: May 1, 2015
• Deposit Date: Aug 17, 2017
• Publicly Available Date: Aug 17, 2017
• Journal: Diabetes
• Print ISSN: 0012-1797
• Electronic ISSN: 1939-327X
• Publisher: American Diabetes Association
• Peer Reviewed: Peer Reviewed
• Volume: 64
• Issue: 5
• DOI: https://doi.org/10.2337/db14-0961
• Public URL: https://nottingham-repository.worktribe.com/output/748657
• Publisher URL: http://diabetes.diabetesjournals.org/content/64/5/1615