R. Vettor et al., INDUCTION AND REVERSIBILITY OF AN OBESITY SYNDROME BY INTRACEREBROVENTRICULAR NEUROPEPTIDE-Y ADMINISTRATION TO NORMAL RATS, Diabetologia, 37(12), 1994, pp. 1202-1208
Citations number
38
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
Intracerebroventricular neuropeptide Y (NPY) administration to normal
rats for 7 days produced a sustained, threefold increase in food intak
e, resulting in a body weight gain of more than 40 g. Basal plasma ins
ulin and triglyceride levels were increased in NPY-treated compared to
vehicle-infused rats by about four- and two-fold, respectively. The g
lucose utilization index of white adipose tissue, measured by the labe
lled 2-deoxy-D-glucose technique was four times higher in NPY-treated
rats compared to controls. This change was accompanied by an increase
in the insulin responsive glucose transporter protein (GLUT 4). In mar
ked contrast, muscle glucose utilization was decreased in NPY-treated
compared to vehicle-infused animals. This change was accompanied by an
increase in triglyceride content. When NPY-treated rats were prevente
d from overeating, there was no decrease in muscle glucose uptake, nor
was there an increase in muscle triglyceride content. This suggests t
hat muscle insulin resistance of ad libitum-fed NPY-treated rats is du
e to a glucose-fatty acid (Randle) cycle. When intracerebroventricular
NPY administration was stopped and rats kept without any treatment fo
r 7 additional days, all the abnormalities brought about by the neurop
eptide were normalized. A tonic central effect of NPY is therefore nee
ded to elicit and maintain most of the hormonal and metabolic abnormal
ities observed in the present study. Such abnormalities are analogous
to those seen in the dynamic phase of obesity syndromes in which high
hypothalamic NPY levels have been reported.