Central regulation of food intake and reproduction
Author(s)
Beale, Kylie Emma Louise
Type
Thesis
Abstract
The work described in this thesis investigates the actions of hypothalamic neuropeptides
involved in the control of energy homeostasis and reproduction.
Cerebellin 1 (Cbln1) is a 16-amino acid peptide abundantly expressed in the cerebellum and the
hypothalamus. I have shown that Cbln1 increases food intake when administered centrally to
rats, and that this effect may be partly mediated by neuropeptide Y. I have also demonstrated that
Cbln1 mRNA expression within the ventromedial nucleus of the hypothalamus is up-regulated
following a 48-hour fast, suggesting that Cbln1 may have a physiological role in the control of
food intake.
In addition to hypothalamic centres, the reward system has an important role in the control of
feeding. The melanocortin system has a well characterised role in the homeostatic control of
food intake. My work suggests that the melanocortin system may also have a previously
unknown role within the ventral tegmental area (VTA) in the hedonic control of feeding. Intra-
VTA administration of a melanocortin agonist reduced, whereas an antagonist increased, food
intake in rats. My work suggests that the VTA melanocortin system may act upstream of
dopamine signalling to influence feeding.
Kisspeptin is a hypothalamic neuropeptide with a crucial role in reproduction. The hypothalamus
contains two populations of kisspeptin neurones, located in the arcuate nucleus (Arc) and in the
anteroventral periventricular nucleus. The physiological role of these two populations is
unknown. I used recombinant adeno-associated virus (rAAV) to suppress kisspeptin expression
within the Arc in female rats. Animals injected bilaterally into the Arc with rAAV-kisspeptin
antisense had significantly fewer oestrous cycles, and an increase in oestrous cycle length,
compared to controls.
In summary, these studies have identified novel roles for Cbln1 and the melanocortin system in
the control of food intake, and have demonstrated the importance of Arc kisspeptin signalling in
the regulation of reproduction.
involved in the control of energy homeostasis and reproduction.
Cerebellin 1 (Cbln1) is a 16-amino acid peptide abundantly expressed in the cerebellum and the
hypothalamus. I have shown that Cbln1 increases food intake when administered centrally to
rats, and that this effect may be partly mediated by neuropeptide Y. I have also demonstrated that
Cbln1 mRNA expression within the ventromedial nucleus of the hypothalamus is up-regulated
following a 48-hour fast, suggesting that Cbln1 may have a physiological role in the control of
food intake.
In addition to hypothalamic centres, the reward system has an important role in the control of
feeding. The melanocortin system has a well characterised role in the homeostatic control of
food intake. My work suggests that the melanocortin system may also have a previously
unknown role within the ventral tegmental area (VTA) in the hedonic control of feeding. Intra-
VTA administration of a melanocortin agonist reduced, whereas an antagonist increased, food
intake in rats. My work suggests that the VTA melanocortin system may act upstream of
dopamine signalling to influence feeding.
Kisspeptin is a hypothalamic neuropeptide with a crucial role in reproduction. The hypothalamus
contains two populations of kisspeptin neurones, located in the arcuate nucleus (Arc) and in the
anteroventral periventricular nucleus. The physiological role of these two populations is
unknown. I used recombinant adeno-associated virus (rAAV) to suppress kisspeptin expression
within the Arc in female rats. Animals injected bilaterally into the Arc with rAAV-kisspeptin
antisense had significantly fewer oestrous cycles, and an increase in oestrous cycle length,
compared to controls.
In summary, these studies have identified novel roles for Cbln1 and the melanocortin system in
the control of food intake, and have demonstrated the importance of Arc kisspeptin signalling in
the regulation of reproduction.
Date Issued
2011
Date Awarded
2011-09
Advisor
Dhillo, Waljit
Murphy, Kevin
Sponsor
Jean Shanks Foundation
Creator
Beale, Kylie Emma Louise
Publisher Department
Medicine: Endocrinology and Metabolic Medicine
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)