CHRONIC INTRACEREBROVENTRICULAR NEUROPEPTIDE-Y ADMINISTRATION TO NORMAL RATS MIMICS HORMONAL AND METABOLIC CHANGES OF OBESITY

Chronic intracerebroventricular (icv) administration of neuropeptide-Y (NPY ; 10 mug/day) was performed in normal female rats to investigate its hormonal and metabolic consequences. Intracerebroventricular NPY produced hyperphagia, increased basal insulinemia, as well as liver an d adipose tissue lipogenic activity. It also increased basal morning c orticosteronemia. When NPY-induced hyperphagia was prevented by pair-f eeding, the icv NPY treatment resulted in the same increases in basal insulinemia and corticosteronemia, and liver and white adipose tissue lipogenesis was still higher than that in respective controls. Under t he ad libitum and pair-feeding conditions, icv NPY stimulated glucose uptake as well as total lipoprotein lipase activity in white adipose t issue; it resulted in an increased total activity of hepatic and white adipose tissue acetyl coenzyme-A-carboxylase. As all hormonal and met abolic changes elicited by icv NPY remained present (at the same or to a lesser extent depending upon the parameter considered) when hyperph agia was prevented by pair-feeding, it was, thus, shown that icv NPY p er se induces peripheral hormonal and metabolic alterations via effere nt routes, which remain to be determined. The effects of icv NPY repor ted in this study are similar to the defects observed in the early pha se of genetic obesity in rodents, the hypothalamus of which has increa sed NPY levels. NPY could, thus, be of relevance in the occurrence of genetically induced obesity.