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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Vydáno v:	JCI insight Ročník 6; číslo 10
Hlavní autoři:	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.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States American Society for Clinical Investigation 24.05.2021 American Society for Clinical investigation
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2379-3708 2379-3708
DOI:	10.1172/jci.insight.145346