Hypothalamic NPY status during positive energy balance and the effects of the NPY antagonist, BW1229U91, on the consumption of highly palatable energy-rich diet

Widdowson, Peter; Henderson, Lynne; Pickavance, Lucy; Buckingham, Robin E.; Tadayyon, Mohammad; Arch, Jonathan R.S.; Williams, Gareth

doi:10.1016/s0196-9781(99)00044-3

Cited by 33 publications

(12 citation statements)

References 24 publications

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“…78,79 By contrast, 1229U91 did not inhibit either spontaneous food intake in normal rats or after the induction of dietary-induced obesity -both cases in which brain NPY levels are low. 79 The product 1229U91 has high affinity for NPY Y 1 and Y 4 receptors and acts as an antagonist of the former and as an agonist at the latter. 80 Furthermore, 1229U91 has also been shown to interact with high affinity to the NPFF(2) receptor, a neural substrate related to NPY that may also be involved in feeding.…”

Section: Miscellaneous Approaches Ventricular Injection Of the Non-smentioning

confidence: 78%

Appetite suppression based on selective inhibition of NPY receptors

Chamorro

Della‐Zuana

et al. 2002

Int J Obes

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AIM:The aim of this review is to critically assess available evidence that blockade of the actions of NPY at one of the five NPY receptor subtypes represents an attractive new drug discovery target for the development of an appetite suppressant drug. RESULTS: Blockade of the central actions of NPY using anti-NPY antibodies, antisense oligodeoxynucleotides against NPY and NPY receptor antagonists results in a decrease in food intake in energy-deprived animals. These results appear to show that endogenous NPY plays a role in the control of appetite. The fact that NPY receptors exist as at least five different subtypes raises the possibility that the actions of endogenous NPY on food intake can be adequately dissociated from other effects of the peptide. Current drug discovery has produced a number of highly selective NPY receptor antagonists which have been used to establish the NPY Y 1 receptor subtype as the most critical in regulating short-term food intake. However, additional studies are now needed to more clearly define the relative contribution of NPY acting through the NPY Y 2 and NPY Y 5 receptors in the complex sequence of physiological and behavioral events that underlie the long-term control of appetite. CONCLUSIONS: Blockade of the NPY receptor may produce appetite-suppressing drugs. However, it is too early to state with certainty whether a single subtype selective drug used alone or a combination of NPY receptor selective antagonists used in combination will be necessary to adequately influence appetite regulation.

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Section: Miscellaneous Approaches Ventricular Injection Of the Non-smentioning

confidence: 78%

Appetite suppression based on selective inhibition of NPY receptors

Chamorro

Della‐Zuana

et al. 2002

Int J Obes

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“…The mechanism for the effect is unclear. Among the possibilities are that the 5HT-2c receptor gene is regulated either directly or indirectly by changes in leptin or glucocorticoids, both of which are normally elevated by HF diets (60,61).…”

Section: Discussionmentioning

confidence: 99%

Effects of a High‐Fat Diet and Strain on Hypothalamic Gene Expression in Rats

et al. 2002

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Effects of a high-fat diet and strain on hypothalamic gene expression in rats. Obes Res. 2002;10:1188 -1196. Objective: This study was designed to investigate whether dietary fat and genetic background might differentially alter the expression of hypothalamic genes involved in food intake. Research Methods and Procedures: Three-month-old Osborne-Mendel (OM) and S5B/Pl rats were fed either a high-fat or a low-fat diet for 14 days. mRNA for neuropeptide Y (NPY), corticotrophin-releasing hormone, NPY Y-1 receptor and Y-5 receptor, and serotonin 2c (5-HT2c) receptors were measured using Northern blotting or ribonuclease protection assays. Results: OM rats showed an increased expression of NPY and corticotrophin-releasing hormone compared with S5B/Pl rats. The expression of NPY-Y1 and -Y5 receptor mRNA was significantly higher in the hypothalamus of OM rats compared with S5B/Pl rats. The expression of 5HT-2c receptor mRNA was significantly reduced in both strains of rats eating a high-fat diet when compared with the animals eating the low-fat diet. Discussion: These data suggest that over activity of the NPY system may contribute to the development of obesity in OM rats and that expression of the 5HT-2c receptor gene may be modulated by dietary fat.

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“…Regarding energy sufficiency, there is little difference between normal and excess levels of leptin, in regard to the set-point of appetite-regulating systems in the brain and high levels of leptin in animals of increased adiposity do not provide a feedback signal to reduce food intake [65,66,67]. High levels of adiposity lead to a decrease in NPY mRNA expression in sheep [68] and in diet-induced obese rats [69,70]. In genetically lean and fat mice, NPY mRNA expression in the hypothalamus was not different between groups under normal feeding conditions but was higher in the lean line than in the fat line in a fasted state [71].…”

Section: Discussionmentioning

confidence: 99%

Expression of Genes for Appetite-Regulating Peptides in the Hypothalamus of Genetically Selected Lean and Fat Sheep

et al. 2009

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Background/Aims: The aim was to determine whether genetic selection of sheep for body composition could be accounted for by changes in the level of expression of genes for appetite-regulating peptides in the hypothalamus. We examined gene expression in the hypothalamus of genetically lean, normal and fat ewes (n = 5/group). Methods: Plasma growth hormone (GH) and metabolic indicators were measured and gene expression in brains was quantified by in situ hybridization. Results: Body weight and voluntary food intake (VFI) were similar between groups, but lean and fat animals respectively had low and high indices of adiposity. GH levels were higher in lean and fat animals than in controls. In the arcuate nucleus (ARC), neuropeptide Y (NPY) expression/cell was higher in the lean animals than in normal animals, but overall NPY expression was similar in fat and normal animals. Pro-opiomelanocortin (POMC) and leptin receptor (ObRb) expression in the ARC was similar across groups. Orexin (ORX) and melanin-concentrating hormone (MCH) expression was inversely correlated to adiposity, being higher in lean and lower in fat animals. Conclusion: Expression of genes for orexigenic neuropeptides is altered in a consistent way. Energy expenditure is reduced by MCH but increased by ORX, so increased expression of the latter may cause increased energy expenditure in the lean animals and vice versa in the fat animals.

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Hypothalamic NPY status during positive energy balance and the effects of the NPY antagonist, BW1229U91, on the consumption of highly palatable energy-rich diet

Cited by 33 publications

References 24 publications

Appetite suppression based on selective inhibition of NPY receptors

Appetite suppression based on selective inhibition of NPY receptors

Effects of a High‐Fat Diet and Strain on Hypothalamic Gene Expression in Rats

Expression of Genes for Appetite-Regulating Peptides in the Hypothalamus of Genetically Selected Lean and Fat Sheep

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