Long- and medium-chain fatty acids induce insulin resistance to a similar extent in humans despite marked differences in muscle fat accumulation

J Clin Endocrinol Metab. 2012 Jan;97(1):208-16. doi: 10.1210/jc.2011-1884. Epub 2011 Oct 26.

Abstract

Context: Animal studies revealed that medium-chain fatty acids (MCFA), due to their metabolic characteristics, are not stored in skeletal muscle and may therefore not give rise to potentially hazardous lipid species impeding insulin signaling.

Objective: We here hypothesized that infusion of medium-chain triacylglycerols (MCT) in healthy lean subjects does not lead to ectopic fat accumulation and hence does not result in lipid-induced insulin resistance.

Design and methods: Nine healthy lean male subjects underwent a 6-h hyperinsulinemic-euglycemic clamp with simultaneous infusion of 1) a 100% long-chain triacylglycerols (LCT) emulsion, 2) a 50/50% MCT/LCT emulsion, or 3) glycerol in a randomized crossover design. Muscle biopsies were taken before and after each clamp.

Results: MCT/LCT infusion raised plasma free fatty acid levels to a similar level compared with LCT infusion alone. Despite elevated free fatty acid levels, intramyocellular triacylglycerol (IMTG) levels were not affected by the MCT/LCT emulsion, whereas LCT infusion resulted in an approximately 1.6-fold increase in IMTG. These differences in muscle fat accumulation did not result in significant differences in lipid-induced insulin resistance between LCT (-28%, P = 0.003) and MCT/LCT (-20%, P < 0.001). Total skeletal muscle ceramide content as well as lactosyl- and glucosylceramide levels were not affected by any of the interventions. In addition, the distribution pattern of all ceramide species remained unaltered.

Conclusions: Although we confirm that MCFA do not lead to ceramide and IMTG accumulation in skeletal muscle tissue in humans, they do induce insulin resistance. These results indicate that, in humans, MCFA may not be beneficial in preventing peripheral insulin resistance.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biopsy
  • Body Composition / drug effects
  • Calorimetry, Indirect
  • Cross-Over Studies
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology
  • Fat Emulsions, Intravenous / pharmacology
  • Fatty Acids / blood
  • Fatty Acids / chemistry
  • Fatty Acids / metabolism
  • Fatty Acids / pharmacology*
  • Glucose Clamp Technique
  • Humans
  • Insulin Resistance / physiology*
  • Lipid Metabolism / drug effects*
  • Male
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Oxidation-Reduction / drug effects
  • Young Adult

Substances

  • Fat Emulsions, Intravenous
  • Fatty Acids