Neuropeptide Y and Prenatal Stress: NPY's role in early programming for Obesity and Anxiety in Adulthood

Prenatal stress predisposes humans and animals to psychological and metabolic disturbances in adulthood, however, the process by which it exerts its long‐lasting effects is not fully understood. We studied long‐term effects of prenatal stress on anxiety, stress response, and reaction to a high fat (HF) diet during adulthood. Neuropeptide Y (NPY), an endogenous orexigenic and anxiolytic compound, may play a role in the development of anxiety, obesity, and dysregulation of the HPA axis in adulthood. During pregnancy, we subjected mice to prenatal stress using a Low Protein Diet (LPD) followed by 9 weeks of post‐weaning HF diet. Both male and female LPD offspring were born smaller, although the LPD males grew at a faster rate on HF diet than their controls. By 9 weeks they developed abdominal adiposity and impaired glucose tolerance, while females did not. Y2R was up‐regulated and Y1 down‐regulated in the visceral fat in the LPD‐stressed females at weaning. Thus, prenatal stress appears to promote anxiety and accelerate development of obesity when offspring are exposed to over‐nutrition in adulthood. This may be due to prenatal stress‐induced lowering of NPY levels in amygdala and other stress‐responsive areas, as seen in chronically stressed mice on HF diet. A comparison of central NPY and Y2R expression is currently in progress.