Effects of serum irisin, neuregulin 4, and weight management on obese adolescent girls with polycystic ovary syndrome

Abstract

The study is aimed at investigating the association of serum irisin、Neuregulin 4 (NRG4), and Anti-müllerian hormone (AMH) with adolescent obesity with Polycystic ovary syndrome (PCOS) and the efficacy of weight management interventions. Serum levels of irisin, NRG4, AMH, sex steroid hormone, body mass index (BMI), serum insulin, and C-peptide were measured in 52 obese adolescent girls with PCOS (PCOS group) and 43 obese adolescent girls without PCOS (non-PCOS group). The levels of AMH, NRG4, serum irisin, sex steroid hormones, BMI, serum insulin, and C-peptide were evaluated in obese PCOS girls before and after one year weight management. The levels of AMH, serum insulin, NRG4, and total testosterone of PCOS group were significantly higher than those of non-PCOS group. On the contrary, serum irisin and serum C-peptide in PCOS group was significantly lower than that in non-PCOS group. The levels of fat mass, percent body fat, total testosterone, AMH, NRG4, and serum insulin in the obese girls with PCOS showed significant decreases compared with before weight management intervention. On the contrary, after one year of body weight management intervention, serum irisin and serum C-peptide was significantly increased. Adolescent obesity complicated with PCOS is significantly associated with glucose and lipid metabolism and sex steroid hormone disorders, but the exact pathophysiological and clinical features are highly variable. Weight management intervention can significantly improve the clinical symptoms and hematological indicators, serum irisin and NRG4 can be used as two essential biomarkers for evaluating weight management.

Serum neuregulin 4 is negatively correlated with insulin sensitivity in humans and impairs mitochondrial respiration in HepG2 cells

“…Importantly, the relationship of NRG4 with insulin sensitivity remained significant after controlling for age, BMI, sex and hsCRP. In line with the current study, increased levels of serum NRG4 in insulin resistance-associated diseases, such as type 2 diabetes ( Kang et al, 2016 ; Chen et al, 2017a ; Kurek Eken et al, 2018 ; Wang et al, 2019c ; Kocak et al, 2019 ) and polycystic ovary syndrome ( Kurek Eken et al, 2019 ; Cao and Hu, 2021 ) have been reported. In contrast, a recent study described low levels of NRG4 in patients with type 2 diabetes in association to microalbuminuria ( Kocak et al, 2020 ), suggesting NRG4 as a putative marker of microvascular dysfunction.…”

Exploring Adipsin, Irisin, and Osteopontin as Biomarkers in Polycystic Ovary Syndrome and Their Associations with Metabolic Alterations: A prospective, case-control study

“…Others found reduced irisin levels in obese PCOS patients (13). Notably, serum irisin levels of obese PCOS women were signi cantly lower than those of non-obese PCOS patients (9,13). Behboudi-Gandevani et al (6) found that irisin has no association with BMI in women with or without PCOS.…”

Review of Novel Potential Insulin Resistance Biomarkers in PCOS Patients—The Debate Is Still Open

“…Additionally, circulating NRG4 was significantly associated with insulin resistance indicators, markers of obesity, and hormonal levels [ 139 ]. The most recent study investigating the impact of weight reduction on serum NRG4 levels in obese adolescent girls with PCOS [ 31 ] has also confirmed a higher initial NRG4 level in overweight patients [ 31 ]. In addition, the study showed that even a short (one-year-long) lifestyle intervention, including change of diet, increased physical activity and avoidance of sedentary behavior may enable to obtain NRG4 levels comparable to healthy control levels from the beginning of the study [ 31 ].…”

“…The aforementioned studies have emphasized the association of NRG4 with metabolic disorders: obesity seems to trigger secretion of NR4, and its high levels might be a form of adjustment to the low-grade chronic inflammation in PCOS; however, further research is required [ 31 , 137 , 139 ].…”