A Lipidomics Analysis of the Relationship Between Dietary Fatty Acid Composition and Insulin Sensitivity in Young Adults

  1. Deborah M. Muoio4,5,6
  1. 1Department of Pediatrics, University of Vermont, Burlington, Vermont
  2. 2Department of Medicine, University of Vermont, Burlington, Vermont
  3. 3Department of Medical Biostatistics, University of Vermont, Burlington, Vermont
  4. 4Stedman Nutrition and Metabolism Center, Duke University, Durham, North Carolina
  5. 5Department of Medicine, Duke University, Durham, North Carolina
  6. 6Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina
  7. 7Pennington Biomedical Research Center, Baton Rouge, Louisiana
  1. Corresponding author: C. Lawrence Kien, cl.kien{at}


Relative to diets enriched in palmitic acid (PA), diets rich in oleic acid (OA) are associated with reduced risk of type 2 diabetes. To gain insight into mechanisms underlying these observations, we applied comprehensive lipidomic profiling to specimens collected from healthy adults enrolled in a randomized, crossover trial comparing a high-PA diet to a low-PA/high-OA (HOA) diet. Effects on insulin sensitivity (SI) and disposition index (DI) were assessed by intravenous glucose tolerance testing. In women, but not men, SI and DI were higher during HOA. The effect of HOA on SI correlated positively with physical fitness upon enrollment. Principal components analysis of either fasted or fed-state metabolites identified one factor affected by diet and heavily weighted by the PA/OA ratio of serum and muscle lipids. In women, this factor correlated inversely with SI in the fasted and fed states. Medium-chain acylcarnitines emerged as strong negative correlates of SI, and the HOA diet was accompanied by lower serum and muscle ceramide concentrations and reductions in molecular biomarkers of inflammatory and oxidative stress. This study provides evidence that the dietary PA/OA ratio impacts diabetes risk in women.


  • Received March 23, 2012.
  • Accepted October 5, 2012.

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