title: Adaptive responses in hypothalamic neuropeptide Y in the face of prolonged high-fat feeding in the rat.
abstract: While a dysregulation in neuropeptide Y (NPY) signaling has been described in rodent models of obesity, few studies have investigated the time-course of changes in NPY content and responsiveness during development of diet-induced obesity. Therefore we investigated the effect of differing lengths (2-17 weeks) of high-fat diet on hypothalamic NPY peptide content, release and NPY-induced hyperphagia. Male Sprague-Dawley rats (211 +/- 3 g) were fed either a high-fat diet (30% fat) or laboratory chow (5% fat). Animals were implanted with intracerebroventricular cannulae to investigate feeding responses to NPY (0.5 nmol, 1 nmol) after 4 or 12 weeks of diet. At the earlier stage of obesity, NPY-induced hyperphagia was not altered; however, animals maintained on the high-fat diet for the longer duration were hyper-responsive to NPY, compared to chow-fed control rats (p < 0.05). Overall, hypothalamic NPY peptide content tended to be decreased from 9 to 17 weeks of diet (p < 0.05). Total hypothalamic NPY content was negatively correlated with plasma leptin concentration (p < 0.05), suggesting the hypothalamic NPY system remains responsive to leptin's inhibitory signal. In addition, hypothalamic NPY overflow was significantly reduced in high-fat fed animals (p < 0.05). Together these results suggest a reduction in hypothalamic NPY activity in high-fat fed animals, perhaps in an attempt to restore energy balance.
authors.affiliation: Neuroendocrine Laboratory, Department of Pharmacology, The University of Melbourne, Victoria, Australia.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Hansen
authors.forename: Valentina
authors.initials: V
authors.lastname: Jovanovska
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Morris
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D001923:Brain Chemistry; D004041:Dietary Fats / Q000494:pharmacology*; D004435:Eating / Q000502:physiology; D006963:Hyperphagia / Q000139:chemically induced / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D004041:Dietary Fats; D009478:Neuropeptide Y