Gan, Hoong-Wei;
(2020)
Quantification of appetite-regulating hormones in children with hypothalamic and common obesity.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Background. Current understanding of the appetite-regulating neuroendocrine circuitry remains incomplete, and efficacious treatments for both common and hypothalamic obesity (HyOb) are lacking. Concurrently, the expanded role of oxytocin (OXT) in energy homeostasis and human behaviour is beginning to be understood. Objectives. To optimise and translate an OXT enzyme immunoassay (EIA) to elucidate whether there were any unique differences in the plasma endocrine milieu in patients with HyOb. Methods. Optimisation work was carried out using EIAs with polyclonal and monoclonal secondary antibodies. Obese (BMI>+2 SDS) and lean (BMI≤+2 SDS) children with (HyOb and HyLean) and without (Ob and Lean) hypothalamic disorders (septo-optic dysplasia or suprasellar tumours) were phenotyped using the Dykens’ Hyperphagia Questionnaire Score (DHQS). Plasma concentrations of leptin, insulin, OXT, BDNF, αMSH, acylated ghrelin, AgRP and copeptin were measured. Results. Solid phase extraction demonstrated markedly variable OXT recovery, and potentially increased rather than decreased interference. A polyclonal secondary antibody-containing EIA showed significant cross-reactivity with several peptides in human plasma compared to a monoclonal secondary antibody-containing EIA. Of the 122 children recruited (50 HyOb, 29 HyLean, 24 Ob, 19 Lean, mean age 11.3±3.9 years) there were no differences in DHQS or hormone concentrations between HyOb and Ob groups. Obesity was associated with compensatorily increased leptin and insulin, and decreased ghrelin and AgRP concentrations. More rapidly increasing BMI was independently associated with a younger age and lower plasma αMSH concentrations. OXT concentrations did not show any correlation with BMI or DHQS. Conclusion. The use of plasma extraction processes and EIAs in the literature needs re-examination. The plasma endocrine milieu in HyOb vs. common obesity does not differ, with a compensatory increase in anorexigens and decrease in orexigens. Lower plasma αMSH was associated with more rapid weight gain, suggesting that MC4R agonists may be a therapeutic option in all forms of obesity.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Quantification of appetite-regulating hormones in children with hypothalamic and common obesity |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| Keywords: | Obesity, Hypothalamus, Pituitary, Brain Tumour, Septa-Optic dysplasia, Appetite, Weight, Oxytocin, Leptin, Insulin, aMSH, BDNF, AgRP, Ghrelin, Copeptin, ELISA |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10107253 |
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