Aims: Neuregulin 4 has recently been recognized as a novel adipokine secreted by brown adipose tissue (BAT), with beneficial effects on murine insulin resistance and hepatic steatosis. Yet, thus far, neither regulation of neuregulin 4 in gestational diabetes mellitus (GDM) nor its longitudinal changes in the peripartum period have been elucidated.
Methods: Circulating neuregulin 4 levels were measured by ELISA in 74 women with GDM and 74 healthy, gestational-age-matched controls. Also, neuregulin 4 was quantified during pregnancy and compared with postpartum levels in a follow-up study of 25 women with previous GDM and 25 healthy control women.
Results: Women with GDM had lower median serum levels of the novel BAT-secreted adipokine neuregulin 4 (3.0μg/L) compared with healthy (non-GDM) pregnant controls (3.5μg/L; P=0.020), and the area under the glucose curve (AUCGlucose) was an independent and negative predictor of circulating neuregulin 4 (P=0.033). Also, median postpartum serum concentrations of neuregulin 4 (3.2μg/L) were not significantly different from prepartum levels (2.8μg/L; P=0.328). In addition, neuregulin 4 was positively and independently associated with irisin (P=0.009), but not other BAT-secreted adipokines.
Conclusion/interpretation: Women with GDM have significantly lower circulating neuregulin 4 levels compared with healthy pregnant controls, and the AUCGlucose is negatively and independently associated with neuregulin 4 during pregnancy. Neuregulin 4 is positively correlated with irisin during pregnancy, as well as in a longitudinal fashion. Future studies are now needed to better elucidate the precise pathomechanisms of the regulation of BAT-secreted adipokines during pregnancy.
Keywords: Adipokine; Brown adipose tissue; Gestational diabetes mellitus; Insulin resistance; Neuregulin 4; Pregnancy.
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