Proteomic Analysis of Cerebrospinal Fluid from Obese Women with Idiopathic Intracranial Hypertension: A New Approach for Identifying New Candidates in the Pathogenesis of Obesity

Abstract

Body weight control is tightly regulated in the hypothalamus. The inaccessibility of human brain tissue can be partially solved by using cerebrospinal fluid (CSF) as a tool for assessing the central nervous system's production of orexigen and anorexigen factors. Using proteomic analysis, the present study investigated the differentially displayed proteins in human CSF from obese and non-obese subjects. We designed a case-control study conducted in a reference hospital where eight obese (cases) and eight non-obese (controls) women with idiopathic intracranial hypertension were included. Intracranial hypertension was normalised through the placement of a ventriculo- or lumboperitoneal shunt in the 12 months before their inclusion in the study. Isotope-coded protein label (for proteins > 10 kDa) and label-free liquid chromatography (for proteins < 10 kDa) associated with mass spectrometry analysis were used. Eighteen differentially expressed proteins were identified. Many of them fall into three main groups: inflammation (osteopontin, fibrinogen γ and β chain, α1 acid glycoprotein 2 and haptoglobin), neuroendocrine mediators (neurosecretory protein VGF, neuroendocrine protein 7B2, chromogranin-A and chromogranin B), and brain plasticity (testican-1, isoform 10 of fibronectin, galectin-3 binding protein and metalloproteinase inhibitor type 2). The differential production of osteopontin, neurosecretory protein VGF, chromogranin-A and fibrinogen γ chain was further confirmed by either enzyme-linked immunosorbent assay or western blotting. In conclusion, we have identified potential candidates that could be involved in the pathogenesis of obesity. Further studies aiming to investigating the precise role of these proteins in the pathogenesis of obesity and their potential therapeutic implications are needed.