Caitlyn Nguyen-Ngo1,2, Jane C Willcox3, Martha Lappas1,2. 1. Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, 3084, Victoria, Australia. 2. Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, 3084, Victoria, Australia. 3. School of Allied Health, College of Science, Health and Engineering, La Trobe University, Bundoora, 3086, Victoria, Australia.
Abstract
SCOPE: Gestational diabetes mellitus (GDM), which affects up to 20% of pregnant women, is associated with maternal peripheral insulin resistance, low-grade inflammation, and oxidative stress. The flavonoid naringenin has potent anti-diabetic, anti-inflammatory, and anti-oxidative properties; however, its effects in GDM remain unknown. The study aimed to determine the effects of naringenin on glucose metabolism, inflammation, and oxidative stress associated with GDM both in vitro and in vivo. METHODS AND RESULTS: In vitro, human tissue samples obtained at term elective Caesarean section are stimulated with tumour necrosis factor alpha (TNF) to develop a GDM-like environment. Naringenin treatment significantly improves TNF-impaired glucose uptake in skeletal muscle. In placenta and visceral adipose tissue (VAT), naringenin significantly reduces expression of pro-inflammatory cytokines and chemokines and increases antioxidant mRNA expression. Mechanistically, naringenin suppresses nuclear factor κB activation. In vivo, pregnant heterozygous db/+ mice are used to model GDM. Daily intraperitoneal injections of GDM mice with naringenin from gestational day 10-17 significantly improve glucose tolerance, reduces IL1A mRNA expression, and increases antioxidant mRNA expression in placenta, VAT, and subcutaneous adipose tissue. CONCLUSION: Naringenin is shown to improve insulin sensitivity, inflammation, and oxidative stress associated with GDM and shows promise as a novel preventive therapeutic.
SCOPE: Gestational diabetes mellitus (GDM), which affects up to 20% of pregnant women, is associated with maternal peripheral insulin resistance, low-grade inflammation, and oxidative stress. The flavonoidnaringenin has potent anti-diabetic, anti-inflammatory, and anti-oxidative properties; however, its effects in GDM remain unknown. The study aimed to determine the effects of naringenin on glucose metabolism, inflammation, and oxidative stress associated with GDM both in vitro and in vivo. METHODS AND RESULTS: In vitro, human tissue samples obtained at term elective Caesarean section are stimulated with tumour necrosis factor alpha (TNF) to develop a GDM-like environment. Naringenin treatment significantly improves TNF-impaired glucose uptake in skeletal muscle. In placenta and visceral adipose tissue (VAT), naringenin significantly reduces expression of pro-inflammatory cytokines and chemokines and increases antioxidant mRNA expression. Mechanistically, naringenin suppresses nuclear factor κB activation. In vivo, pregnant heterozygous db/+ mice are used to model GDM. Daily intraperitoneal injections of GDM mice with naringenin from gestational day 10-17 significantly improve glucose tolerance, reduces IL1A mRNA expression, and increases antioxidant mRNA expression in placenta, VAT, and subcutaneous adipose tissue. CONCLUSION:Naringenin is shown to improve insulin sensitivity, inflammation, and oxidative stress associated with GDM and shows promise as a novel preventive therapeutic.
Authors: Ricardo Wesley Alberca; Franciane Mouradian Emidio Teixeira; Danielle Rosa Beserra; Emily Araujo de Oliveira; Milena Mary de Souza Andrade; Anna Julia Pietrobon; Maria Notomi Sato Journal: Front Immunol Date: 2020-09-25 Impact factor: 7.561