S Kralisch1, A Hoffmann2, J Kratzsch3, M Blüher2, M Stumvoll2, M Fasshauer1, T Ebert4. 1. Department of Endocrinology and Nephrology, University of Leipzig, 04103 Leipzig, Germany; Leipzig University Medical Center, IFB Adiposity Diseases, 04103 Leipzig, Germany. 2. Department of Endocrinology and Nephrology, University of Leipzig, 04103 Leipzig, Germany. 3. Institute of Laboratory Medicine, University of Leipzig, 04103 Leipzig, Germany. 4. Department of Endocrinology and Nephrology, University of Leipzig, 04103 Leipzig, Germany; Leipzig University Medical Center, IFB Adiposity Diseases, 04103 Leipzig, Germany. Electronic address: Thomas.ebert@medizin.uni-leipzig.de.
Abstract
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.
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.
Authors: Erind Gjermeni; Anna S Kirstein; Florentien Kolbig; Michael Kirchhof; Linnaeus Bundalian; Julius L Katzmann; Ulrich Laufs; Matthias Blüher; Antje Garten; Diana Le Duc Journal: Biomolecules Date: 2021-09-29