Five-hour fatty acid elevation increases muscle lipids and impairs glycogen synthesis in the rat

Metabolism. 1998 Sep;47(9):1121-6. doi: 10.1016/s0026-0495(98)90287-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fatty Acids, Nonesterified / blood*
  • Glucose / metabolism
  • Glycogen / biosynthesis*
  • Insulin Resistance
  • Lipid Metabolism*
  • Male
  • Muscle, Skeletal / metabolism*
  • Rats
  • Rats, Wistar
  • Time Factors


  • Fatty Acids, Nonesterified
  • Glycogen
  • Glucose