title: Lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men.
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-(2)H5]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.
authors.affiliation: Medical Research Council/Arthritis Research UK Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Nottingham, U.K. francis.stephens@nottingham.ac.uk.
authors.forename: Francis B
authors.initials: FB
authors.lastname: Stephens
authors.affiliation: Medical Research Council/Arthritis Research UK Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Nottingham, U.K.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Chee
authors.affiliation: School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Wall
authors.affiliation: Division of Nutritional Sciences, School of Biosciences, University of Nottingham, Nottingham, U.K.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murton
authors.affiliation: Medical Research Council/Arthritis Research UK Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Nottingham, U.K.
authors.forename: Chris E
authors.initials: CE
authors.lastname: Shannon
authors.affiliation: School for Nutrition, Toxicology and Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Luc J C
authors.initials: LJ
authors.lastname: van Loon
authors.affiliation: Medical Research Council/Arthritis Research UK Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Nottingham, U.K.
authors.forename: Kostas
authors.initials: K
authors.lastname: Tsintzas
mesh_terms: D000596:Amino Acids / Q000494:pharmacology*; D004655:Emulsions / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010743:Phospholipids / Q000494:pharmacology*; D015398:Signal Transduction; D013024:Soybean Oil / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000596:Amino Acids; D004655:Emulsions; D009124:Muscle Proteins; D010743:Phospholipids; C545823:soybean oil, phospholipid emulsion; D013024:Soybean Oil; D005947:Glucose