Role of dorsomedial hypothalamic neuropeptide Y in modulating food intake and energy balance.
Previous studies have suggested that neuropeptide Y (NPY) in the dorsomedial hypothalamus (DMH) serves as an important signaling peptide in the regulation of energy balance. To elucidate such actions, we used the adenoassociated virus (AAV) system to alter Npy gene expression in the DMH and examined the effects of these alterations on food intake and energy balance as well as explored its downstream signaling pathway. We found that AAV-mediated overexpression of NPY in the DMH of lean rats increased food intake and body weight, and exacerbated high-fat diet-induced obesity. Knockdown of NPY expression in the DMH via AAV-mediated RNA interference ameliorated the hyperphagia, obesity, and diabetes of Otsuka Long-Evans Tokushima Fatty (OLETF) rats. NPY knockdown in the DMH produced a nocturnal and meal size-specific feeding effect. Moreover, we found that knockdown of DMH NPY expression in intact rats reduced NPY content in the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus and affected within-meal satiation. DMH NPY knockdown increased the feeding inhibitory and NTS c-Fos responses to peripheral administration of cholecystokinin. Together, these results indicate that DMH NPY plays an important role in modulating food intake and energy balance and its dysregulation causes disordered energy balance leading to obesity.
Yang
Liang
L
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Scott
Karen A
KA
Hyun
Jayson
J
Tamashiro
Kellie L
KL
Tray
Nancy
N
Moran
Timothy H
TH
Bi
Sheng
S
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002461:Cell Line, Transformed; D002766:Cholecystokinin / Q000494:pharmacology; D000229:Dependovirus / Q000502:physiology; D004302:Dorsomedial Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D005951:Glucose Tolerance Test / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D051381:Rats; D020334:Rats, Inbred OLETF / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000378:metabolism; D013997:Time Factors
D009478:Neuropeptide Y; D016760:Proto-Oncogene Proteins c-fos; D049452:Green Fluorescent Proteins; D002766:Cholecystokinin