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

F.B. Stephens*, C. Chee, B.T. Wall, A.J. Murton, C.E. Shannon, L.J. van Loon, K. Tsintzas

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The ability to maintain skeletal muscle mass appears to be impaired in insulin resistant conditions that are characterised by muscle lipid accumulation, such as type 2 diabetes. The present 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 randomised occasions combined with either 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 euglycaemic hyperinsulinemic clamp was commenced ('fed' period). Muscle biopsies 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 mixed muscle fractional synthetic rate increased from the basal to 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.
Original languageEnglish
Pages (from-to)1615-1620
JournalDiabetes
Volume64
Issue number5
DOIs
Publication statusPublished - 1 Jan 2015

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