The Leu7Pro polymorphism of the neuropeptide Y gene regulates free fatty acid metabolism

Metabolism. 2003 May;52(5):643-6. doi: 10.1053/meta.2003.50098.


The Leu7Pro polymorphism in the signal peptide of the preproneuropeptide Y (NPY) has been associated with dyslipidemias and free fatty acid (FFA) levels during exercise. The association of this polymorphism with insulin sensitivity has not been studied. In this study, the Leu7Pro polymorphism was determined in 2 groups of nondiabetic middle-aged subjects (n = 266 and n = 295). Insulin sensitivity was measured with the hyperinsulinemic euglycemic clamp (n = 266) or with an intravenous glucose tolerance test (IVGTT, n = 295). First-phase insulin secretion was determined as insulin area under the curve (AUC) during the first 10 minutes of the IVGTT. FFAs were measured both in the fasting state and during the hyperinsulinemic clamp. The Leu7Pro polymorphism of the NPY gene was not associated with the rates of whole body glucose uptake, insulin sensitivity index, insulin secretion during the IVGTT, or insulin AUC during the oral glucose tolerance test. However, the Pro7 allele was associated with low FFA levels both in the fasting state (P =.043) and during the hyperinsulinemic clamp (P =.003). In conclusion, the Leu7Pro polymorphism of the NPY gene associates with alterations in FFA metabolism but does not have an impact on insulin sensitivity, insulin secretion, or glucose metabolism.

Publication types

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

MeSH terms

  • Alleles
  • Area Under Curve
  • Blood Glucose / metabolism
  • Fatty Acids, Nonesterified / metabolism*
  • Female
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology*
  • Glucose Clamp Technique
  • Glucose Tolerance Test
  • Humans
  • Insulin Resistance / genetics
  • Insulin Resistance / physiology
  • Male
  • Middle Aged
  • Neuropeptide Y / genetics*
  • Neuropeptide Y / physiology*
  • Polymorphism, Genetic / genetics*


  • Blood Glucose
  • Fatty Acids, Nonesterified
  • Neuropeptide Y