title: Five-hour fatty acid elevation increases muscle lipids and impairs glycogen synthesis in the rat.
abstract: Insulin-mediated muscle glycogen synthesis is impaired after several weeks of high-fat feeding in rats, but not by short-term (2-hour) nonesterified fatty acids (NEFA) elevation induced by intravenous triglyceride/heparin infusion (TG/H). We examined whether a longer TG/H infusion induces defective glycogen synthesis. Five-hour hyperinsulinemic (700 pmol/L) euglycemic clamps with either TG/H or saline infusion were performed. TG/H-infused rats developed insulin resistance, but only after 2 to 3 hours. Red gastrocnemius glycogen synthesis rate decreased by 50% (P < .01 v saline) associated with decreased glycogen synthase activity (GSa; assessed at several glucose-6-phosphate [G-6-P] levels; two-way ANOVA, P=.02) and increased muscle TG and total long-chain acyl coenzyme A (LCAC) content (twofold; P < .05 v saline). Thus a 3- to 5-hour NEFA elevation in the rat produced significant impairment of insulin-stimulated muscle glycogen synthesis, associated with muscle lipid accumulation. These effects were similar to those observed after several weeks of fat feeding. The 5-hour TG/H-infused rat is a useful model for studying lipid-induced muscle insulin resistance.
authors.affiliation: Garvan Institute of Medical Research, Sydney, NSW, Australia.
authors.forename: S M
authors.initials: SM
authors.lastname: Chalkley
authors.forename: M
authors.initials: M
authors.lastname: Hettiarachchi
authors.forename: D J
authors.initials: DJ
authors.lastname: Chisholm
authors.forename: E W
authors.initials: EW
authors.lastname: Kraegen
mesh_terms: D000818:Animals; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis*; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D005230:Fatty Acids, Nonesterified; D006003:Glycogen; D005947:Glucose