Characterising the phenotype and impact of adipose in idiopathic intracranial hypertension

Download Statistics

Downloads

Downloads per month over past year

Westgate, Connar Stanley James (2019). Characterising the phenotype and impact of adipose in idiopathic intracranial hypertension. University of Birmingham. Ph.D.

Preview

Westgate2019PhD.pdf
Text - Accepted Version
Available under License All rights reserved.
Download (8MB) | Preview

Abstract

Idiopathic intracranial hypertension (IIH) is a rare disease that primarily affects obese women of reproductive age, characterised by raised intracranial pressure (ICP) and papilloedema that drives chronic debilitating headache and visual loss. The aetiology of IIH is uncertain, however it is clear that weight loss is therapeutic and reduces ICP, headache, and visual morbidity. Novel data has highlighted that female IIH patients have an androgen excess phenotype. However the role of adipose tissue and androgens in the pathogenesis of IIH remains unclear.
Utilising RNA-sequencing, NMR-based metabolomics and secretomic techniques, it has been identified that ex vivo subcutaneous adipose tissue from female IIH patients has features of glucocorticoid excess including increased lipolysis, ribosomal subunit depletion and a preference for lipid synthesis, driven by intra-adipose cortisol accumulation. Moreover, this phenotype is driving hyperleptinaemia in IIH patients. Additionally, a novel in vitro Na+/K+ ATPase activity assay was developed, which demonstrated that testosterone increases Na+/K+ ATPase activity, suggesting capacity to increase ICP.
Together, these data highlight that adipose tissue in IIH has characteristics of glucocorticoid excess, contributing to a specific metabolic phenotype and that testosterone could be driving raised intracranial pressure, highlighting routes for the development of novel therapeutics and treatments for IIH.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):