Systemic and adipocyte transcriptional and metabolic dysregulation in idiopathic intracranial hypertension

BACKGROUNDIdiopathic intracranial hypertension (IIH) is a condition predominantly affecting obese women of reproductive age. Recent evidence suggests that IIH is a disease of metabolic dysregulation, androgen excess, and an increased risk of cardiovascular morbidity. Here we evaluate systemic and ad...

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Veröffentlicht in:JCI insight Jg. 6; H. 10
Hauptverfasser: Westgate, Connar S.J., Botfield, Hannah F., Alimajstorovic, Zerin, Yiangou, Andreas, Walsh, Mark, Smith, Gabrielle, Singhal, Rishi, Mitchell, James L., Grech, Olivia, Markey, Keira A., Hebenstreit, Daniel, Tennant, Daniel A., Tomlinson, Jeremy W., Mollan, Susan P., Ludwig, Christian, Akerman, Ildem, Lavery, Gareth G., Sinclair, Alexandra J.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States American Society for Clinical Investigation 24.05.2021
American Society for Clinical investigation
Schlagworte:
Adipocytes
Adipocytes - metabolism
Adipose tissue
Adipose Tissue - metabolism
Adult
Androgens
Biopsy
Blood Glucose - metabolism
Body composition
Body fat
Body mass index
Cardiovascular diseases
Case-Control Studies
Clinical Medicine
Diabetes
Diabetes mellitus
Disease
Disease resistance
Female
Genotype & phenotype
Glucose
Homeostasis
Humans
Hypertension
Insulin - metabolism
Insulin resistance
Leptin
Leptin - metabolism
Lipogenesis
Mann-Whitney U test
Medical research
Metabolic Diseases - metabolism
Metabolic Diseases - physiopathology
Metabolic disorders
Metabolism
Metabolomics
Middle Aged
Morbidity
Neuroscience
NMR
Nuclear magnetic resonance
Obesity
Obesity - metabolism
Obesity - physiopathology
Ophthalmology
Patients
Phenotypes
Pseudotumor Cerebri - metabolism
Pseudotumor Cerebri - physiopathology
Triglycerides
Weight control
Young Adult
United Kingdom > UK
Obesity
Neuroscience
Ophthalmology
Neurological disorders
ISSN:2379-3708, 2379-3708
Online-Zugang:Volltext
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Zusammenfassung:BACKGROUNDIdiopathic intracranial hypertension (IIH) is a condition predominantly affecting obese women of reproductive age. Recent evidence suggests that IIH is a disease of metabolic dysregulation, androgen excess, and an increased risk of cardiovascular morbidity. Here we evaluate systemic and adipose specific metabolic determinants of the IIH phenotype.METHODSIn fasted, matched IIH (n = 97) and control (n = 43) patients, we assessed glucose and insulin homeostasis and leptin levels. Body composition was assessed along with an interrogation of adipose tissue function via nuclear magnetic resonance metabolomics and RNA sequencing in paired omental and subcutaneous biopsies in a case-control study.RESULTSWe demonstrate an insulin- and leptin-resistant phenotype in IIH in excess of that driven by obesity. Adiposity in IIH is preferentially centripetal and is associated with increased disease activity and insulin resistance. IIH adipocytes appear transcriptionally and metabolically primed toward depot-specific lipogenesis.CONCLUSIONThese data show that IIH is a metabolic disorder in which adipose tissue dysfunction is a feature of the disease. Managing IIH as a metabolic disease could reduce disease morbidity and improve cardiovascular outcomes.FUNDINGThis study was supported by the UK NIHR (NIHR-CS-011-028), the UK Medical Research Council (MR/K015184/1), Diabetes UK, Wellcome Trust (104612/Z/14/Z), the Sir Jules Thorn Award, and the Midlands Neuroscience Teaching and Research Fund.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.145346