title: The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes.
abstract: Peripheral action of irisin improves glucose homeostasis and increases energy expenditure, with no data on a central role of irisin in metabolism. These studies sought to examine 1) presence of irisin in human cerebrospinal fluid (CSF) and banked human hypothalamic tissue, 2) serum irisin in maternal subjects across varying adiposities with or without gestational diabetes (GDM), and 3) their respective neonate offspring. CSF, serum, and neonatal cord serum were collected from 91 pregnant women with and without GDM attending for an elective cesarean section [body mass index (BMI): 37.7 ± 7.6 kg/m(2); age: 32 ± 8.3 yr]. Irisin was assessed by ELISA and correlated with biochemical and anthropometric data. Irisin expression was examined in human hypothalamus by immunohistochemical staining. Serum irisin in pregnant women was significantly lower in nonobese compared with obese and GDM subjects, after adjusting for BMI, lipids, and glucose. Irisin was present in neonatal cord serum (237 ± 8 ng/ml) and maternal CSF (32 ± 1.5 ng/ml). CSF irisin correlated positively with serum irisin levels from nonobese and obese pregnant women (P < 0.01), with CSF irisin significantly raised in GDM subjects (P < 0.05). Irisin was present in human hypothalamic sections in the paraventricular neurons, colocalized with neuropeptide Y. Irisin was detectable in CSF and in paraventricular neurons. Maternal serum irisin was lower in nonobese pregnant women after adjusting for BMI and a number of metabolic parameters. These studies indicate that irisin may have a central role in metabolism in addition to the known peripheral role. Further studies investigating the central action of irisin in human metabolic disease are required.
authors.affiliation: Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Clinical Sciences Research Laboratories, Coventry, United Kingdom;
authors.forename: Milan K
authors.initials: MK
authors.lastname: Piya
authors.forename: Alison L
authors.initials: AL
authors.lastname: Harte
authors.forename: Kavitha
authors.initials: K
authors.lastname: Sivakumar
authors.forename: Gyanendra
authors.initials: G
authors.lastname: Tripathi
authors.forename: Philip D
authors.initials: PD
authors.lastname: Voyias
authors.forename: Sean
authors.initials: S
authors.lastname: James
authors.forename: Shaun
authors.initials: S
authors.lastname: Sabico
authors.forename: Nasser M
authors.initials: NM
authors.lastname: Al-Daghri
authors.forename: Ponnusamy
authors.initials: P
authors.lastname: Saravanan
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Barber
authors.forename: Sudhesh
authors.initials: S
authors.lastname: Kumar
authors.forename: Manu
authors.initials: M
authors.lastname: Vatish
authors.forename: Philip G
authors.initials: PG
authors.lastname: McTernan
mesh_terms: D050154:Adiposity / Q000502:physiology*; D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism; D016640:Diabetes, Gestational / Q000134:cerebrospinal fluid / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000134:cerebrospinal fluid / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D009765:Obesity / Q000134:cerebrospinal fluid / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D015415:Biomarkers; C577593:FNDC5 protein, human; D005353:Fibronectins; D009478:Neuropeptide Y
keywords: gestational diabetes mellitus; irisin; leptin; obesity