Endocrine Abstracts

Idiopathic intracranial hypertension (IIH) is characterised by raised intracranial pressure (ICP) and papilloedema, diagnosed primarily in obese women of reproductive age, with the incidence rising with the global epidemic of obesity. Weight-loss lowers ICP and treats IIH. No mechanism explains the link between obesity and raised ICP. We hypothesise that adipose tissue from IIH patients has a metabolically distinct profile that contributes to raised ICP. Our previous data demonstrates elevated cerebrospinal fluid leptin levels as well as changes in systemic 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity which correlate with ICP. Here we detail the phenotype of subcutaneous (SC) adipose tissue from female IIH patients and healthy age, BMI and gender matched controls. Morphometric analysis showed that IIH and control SC adipose are indistinguishable in terms of cross-sectional area. However, while 11β-HSD1 gene expression was unchanged, LCMS based 11β-HSD1 assays show that when treated with cortisone, SC adipose tissue in IIH is capable of generating more cortisol compared to controls (679±115 vs 234±80 pg pg/h/100 mg; P<0.05, n=6 vs 10). SC adipose cytokine secretion was screened (IL-1β, IL-6, IL-8, IL-10, MCP-1, TNF-α and leptin) and revealed that IIH leptin was elevated compared to controls (8309±1593 vs 2366±431 pg/24h/100 mg; P<0.01, n=11–12). Functional changes were examined by NMR metabolomics and show that IIH SC adipose produces more glycerol compared to controls (186±67 μM vs. 97±25 μM; P<0.05, n=6 vs 6). Furthermore lipid generating amino acids leucine and isoleucine were preferentially consumed by IIH SC adipose vs control, potentially indicative of altered lipid handling and turnover. These data suggest that SC adipose tissue in IIH is metabolically distinct from matched controls. We propose that SC adipose derived factors, such as glucocorticoids and leptin, coupled with changes in lipid turnover may mechanistically contribute to raised ICP and warrants further investigation.