Viral mediated neuropeptide Y expression in the rat paraventricular nucleus results in obesity.
OBJECTIVE
Chronic central administration of neuropeptide Y (NPY) has dramatic effects on energy balance; however, the exact role of the hypothalamic paraventricular nucleus (PVN) in this is unknown. The aim of this study was to further unravel the contribution of NPY signaling in the PVN to energy balance.


METHODS
Recombinant adeno-associated viral particles containing NPY (rAAV-NPY) were injected in the rat brain with coordinates targeted at the PVN. For three weeks, body weight, food intake, endocrine parameters, body temperature, and locomotor activity were measured. Furthermore, effects on insulin sensitivity and expression of NPY, agouti-related protein (AgRP), and pro-opiomelanocortin in the arcuate nucleus were studied.


RESULTS
Food intake was increased specifically in the light period, and dark phase body temperature and locomotor activity were reduced. This resulted in obesity characterized by increased fat mass; elevated plasma insulin, leptin, and adiponectin; decreased AgRP expression in the arcuate nucleus; and decreased insulin sensitivity; whereas plasma corticosterone was unaffected.


CONCLUSIONS
These data suggest that increased NPY expression targeted at the PVN is sufficient to induce obesity. Interestingly, plasma concentrations of leptin and insulin were elevated before a rise in food intake, which suggests that NPY in the PVN influences leptin and insulin secretion independently from food intake. This strengthens the role of the PVN in regulation of energy balance by NPY.
Tiesjema
Birgitte
B
Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
la Fleur
Susanne E
SE
Luijendijk
Mieneke C M
MC
Brans
Maike A D
MA
Lin
En-Ju D
EJ
During
Matthew J
MJ
Adan
Roger A
RA
D000256:Adenoviridae / Q000235:genetics; D052242:Adiponectin / Q000097:blood; D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D001823:Body Composition / Q000235:genetics; D001831:Body Temperature / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D009043:Motor Activity / Q000235:genetics; D009478:Neuropeptide Y / Q000235:genetics / Q000502:physiology*; D009765:Obesity / Q000235:genetics*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism / Q000502:physiology* / Q000821:virology; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection
C515197:AGRP protein, rat; D052242:Adiponectin; D054369:Agouti-Related Protein; D007328:Insulin; D020738:Leptin; D009478:Neuropeptide Y