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Energy homeostasis : crosstalk between adipose tissue and the human hypothalamus
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Kos, Katarina (2007) Energy homeostasis : crosstalk between adipose tissue and the human hypothalamus. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b2232130~S1
Abstract
There is a worldwide epidemic of obesity. Weight rise is a consequence of
continuous positive energy balance which leads to accumulation of body fat.
Recent insights into adipose tissue (AT) biology have led to the conclusion that
the adipocyte is not just a storage depot for triglycerides but also an endocrine
organ. AT secretes proteins, such as leptin, which control central appetite
regulation in the human hypothalamus. In contrast, several other proteins and
neurotransmitters regulate central energy balance, but can also influence AT
metabolism to elicit feedback on fat accumulation. This suggests a close link
between AT and the brain within an AT-to-brain crosstalk system including
feedback circuits. This thesis examines firstly, the potential of crosstalk between
AT and the brain by other adipokines and secondly, the brain-AT crosstalk by
expression of neurotransmitters and their receptors in AT. The study establishes
the presence of the adipokines adiponectin and resistin in human cerebrospinal
fluid and immunohistochemistry showed adiponectin receptors in energy
regulating nuclei of the hypothalamus. Furthermore, this thesis established that the
orexigenic neurotransmitters NPY and ghrelin are secreted by human adipocytes,
where they enhance lipid accumulation. Further, that NPY levels increase with
obesity and its in vitro secretion is enhanced by insulin. This may play an
important role in the pathogenesis of the metabolic syndrome and may induce an
escape of the appetite behaviour towards positive energy balance. Finally, this
thesis highlights the influence of a depot-specific innervation of AT on energy
homeostasis by establishing presence of nicotinic receptors in human adipocytes,
which may play a role in smoking induced changes in adipokine secretion and fat
mass.
In conclusion, this thesis suggests a tight interplay between AT and the brain and
highlights its potential relevance in human pathophysiology.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QP Physiology | ||||
Library of Congress Subject Headings (LCSH): | Adipose tissues -- Physiology, Obesity -- Pathophysiology, Hypothalamus | ||||
Official Date: | July 2007 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Warwick Medical School | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Kumar, Sudhesh ; McTernan, P. G. (Philip G.) ; O'Hare, Paul | ||||
Extent: | xxi, 253 leaves | ||||
Language: | eng |
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