The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes

Abstract

eral 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 Ϯ 7.6 kg/m 2 ; age: 32 Ϯ 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 Ϯ 8 ng/ml) and maternal CSF (32 Ϯ 1.5 ng/ml). CSF irisin correlated positively with serum irisin levels from nonobese and obese pregnant women (P Ͻ 0.01), with CSF irisin significantly raised in GDM subjects (P Ͻ 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.irisin; obesity; gestational diabetes mellitus; leptin EMERGING DATA SUGGEST THAT a newly discovered polypeptide hormone, irisin, a cleaved secreted form of fibronectin type III domain containing 5 (FNDC5), has the potential to increase energy expenditure and improve glucose homeostasis in humans (4,16,31,34). This is particularly significant, since irisin can induce the transformation of white adipocytes into "beige" or "brite" adipocytes, which can ultimately lead to increased mitochondrial respiration (4, 34), with implications for weight loss. Therefore, such studies suggest the potential therapeutic applications of irisin not only in use for weight loss but also to improve glucose metabolism (4). Subsequent research has also revealed that the function of irisin appears to fall beyond its original role noted in muscle (4,9,13,21,23), and the administration of exogenous irisin could theoretically increase energy expenditure during or after weight loss. Recent studies have shown that irisin may also act as an adipokine (21, 25) as well as a potential "neurokine" (9, 12). Although the role of irisin in the brain is unclear, analysis has revealed that FNDC5 knockdown in murine embryonic stem cells reduces neurogenesis (11), whereas pharmacological doses of irisin increase proliferation of mouse hippocampal neuronal cells (20...

Circulating irisin is lower in gestational diabetes mellitus

“…As a large range of circulating irisin was detected by the current reports [5][6][7][8], Fig. 2 The differences of circulating irisin between participants with GDM and healthy control groups There has been only one report, plus ours, that mentioned when GDM was diagnosed [5], and only two studies reported how the patients were treated [5,7].…”

“…If heterogeneity was not 1703. 3 (1354.8-2097.9) ng/mL vs. 1873.8 (1519.8-2294.8) ng/mL, P=0.01) [7], whereas Piya et al did not support this finding (GDM 802±88 ng/mL vs. healthy control 805±53 ng/mL) [8]. These controversial results might mostly be due to the small number of sample sizes, which could affect the power of statistical analysis conducted.…”

Alteration of maternal serum irisin levels in gestational diabetes mellitus

“…To the best of our knowledge, only five studies on the association between irisin and GDM have been reported in the literature [8][9][10][11][12]. In light of the conflicting results of these studies, we also wished to investigate this topic.…”

The Diagnostic Value of Irisin and Visfatin in Experimental Testicular Torsion

“…As determined in various studies, serum irisin levels decrease in type 2 diabetes mellitus (DM) and gestational DM, non-alcoholic hepatic failure and in individuals with lower body mass indices vs. obese individuals and increase in metabolic syndrome (14,(20)(21)(22)(23).…”