Hypothalmic neuropeptide Y in the control of normal and abnormal food intake and metabolism
Hypothalmic neuropeptide Y in the control of normal and abnormal food intake and metabolism
I have investigated the role of hypothalamic peptides, with particular emphasis on neuropeptide Y (NPY), in the regulation of food intake and metabolism. NPY is a peptide neurotransmitter found in several hypothalamic regions involved in the control of food intake. It is the most powerful appetite stimulant known, and its concentration and mRNA rise in food deprived animals, suggesting a physiological role.
In rats with acquired obesity, produced by feeding a palatable diet, I found increased hypothalamic NPY concentrations, but unchanged NPY mRNA, suggesting increased storage and reduced release. Reduced NPY release would be expected to reduce thermogenesis, a recognised change in this model of obesity. The NPY levels in these animals were not altered by administration of the anorectic drug, dexfenfluramine. In contrast, the ob/ob mouse, which has obesity and insulin resistance inherited as an autosomal recessive trait, was found to have a three-fold increase in hypothalamic NPY mRNA, which may be a factor in the development of the obese phenotye.
Hypothalamic NPY is regulated by several hormones and I have demonstrated a reciprocal relationship between stimulation by glucocorticoids, and suppression by insulin. This may be relevant to genetic obesity, where the combination of generalised insulin resistance and high corticosterone levels may explain the observed changes in NPY mRNA. NPY mRNA is increased in the hyperphagia associated with lactation in rodents, and a further increase was found with food deprivation, suggesting a separate population of neurones may be involved in lactation and food deprivation. Given that NPY suppresses LH secretion, it seems likely that reduced LH secretion observed in lactation and food deprivation is related to increased hypothalamic NPY activity.
University of Southampton
Wilding, John Paul Howard
659023b0-0586-4eb4-b689-82fdc448d530
1994
Wilding, John Paul Howard
659023b0-0586-4eb4-b689-82fdc448d530
Wilding, John Paul Howard
(1994)
Hypothalmic neuropeptide Y in the control of normal and abnormal food intake and metabolism.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
I have investigated the role of hypothalamic peptides, with particular emphasis on neuropeptide Y (NPY), in the regulation of food intake and metabolism. NPY is a peptide neurotransmitter found in several hypothalamic regions involved in the control of food intake. It is the most powerful appetite stimulant known, and its concentration and mRNA rise in food deprived animals, suggesting a physiological role.
In rats with acquired obesity, produced by feeding a palatable diet, I found increased hypothalamic NPY concentrations, but unchanged NPY mRNA, suggesting increased storage and reduced release. Reduced NPY release would be expected to reduce thermogenesis, a recognised change in this model of obesity. The NPY levels in these animals were not altered by administration of the anorectic drug, dexfenfluramine. In contrast, the ob/ob mouse, which has obesity and insulin resistance inherited as an autosomal recessive trait, was found to have a three-fold increase in hypothalamic NPY mRNA, which may be a factor in the development of the obese phenotye.
Hypothalamic NPY is regulated by several hormones and I have demonstrated a reciprocal relationship between stimulation by glucocorticoids, and suppression by insulin. This may be relevant to genetic obesity, where the combination of generalised insulin resistance and high corticosterone levels may explain the observed changes in NPY mRNA. NPY mRNA is increased in the hyperphagia associated with lactation in rodents, and a further increase was found with food deprivation, suggesting a separate population of neurones may be involved in lactation and food deprivation. Given that NPY suppresses LH secretion, it seems likely that reduced LH secretion observed in lactation and food deprivation is related to increased hypothalamic NPY activity.
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Published date: 1994
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Local EPrints ID: 458443
URI: http://eprints.soton.ac.uk/id/eprint/458443
PURE UUID: 688b00ce-0c87-4364-8524-83f2e274b8ac
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Date deposited: 04 Jul 2022 16:49
Last modified: 23 Jul 2022 00:21
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Author:
John Paul Howard Wilding
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