Neuropeptide Y: a novel link between the neuroendocrine system and cholesterol metabolism

High serum total and low-density lipoprotein (LDL) cholesterol levels const itute the main risk factor for atherosclerotic vascular diseases. Both gene tic and environmental factors are involved in the regulation of serum chole sterol levels. Neuropeptide Y (NPY), which is widely expressed in both the central and peripheral nervous systems, is known to regulate food intake an d energy balance but its role in cholesterol metabolism has remained almost untouched in former literature. A newly discovered association between a l eucine(7)-to-proline(7) polymorphism (Pro(7)) in the signal peptide of NPY and a high cholesterol level may provide new ideas for the genetic regulati on of cholesterol metabolism. The presence of the Pro(7) in NPY results in serum total cholesterol levels 0.6-1.4 mmol/L higher compared with subjects without this gene variant. The Pro(7) in NPY was detected in 14% of Finns but only in 6% of Dutchmen, and its impact on serum cholesterol concentrati on seems to be stronger in obese than in normal-weight subjects. At least a mong Finns, the Pro(7) in NPY is one of the strongest genetic factors ident ified thus far affecting serum cholesterol levels.