Gestational Diabetes Mellitus (GDM) has an effect on the health of pregnant women and fetuses.
Procyanidins (PA) is a
flavonoid with anti-diabetic activity, but its effects and mechanisms on GDM have not been defined. Herein, we studied further the functions and mechanisms of PA on
insulin resistance (IR) in GDM mice, as well as on postpartum and offspring mice. GDM mice model was built by feeding a high-fat-high-
sucrose diet, and PA intervention (27.8 mg/kg/d) was performed from 4 weeks before pregnancy to delivery. Intestinal flora deficient (IFD) mice model was established by broad spectrum
antibiotics. PA decreased the
gestational weight gain, and the levels of fasting
blood glucose,
insulin, homeostasis model of assessment for IR index, yet increased the levels of HOMA for
insulin sensitivity index. Interestingly, in IFD mice the effect of PA on improving IR was significantly weakened. PA inhibited
inflammation by decreasing the levels of
IL-6, TNF-α,
IL-17 and CRP, which also been blocked in the IFD mice. Moreover, PA improved glycometabolism and reduced the secretion of inflammatory factors and hepatic
inflammation infiltration of mice at 4 weeks postpartum, but had no significant effect on offspring mice. Mechanistically, PA treatment suppressed the nuclear factor-κB (NF-κB) p65 nuclear translocation and
nucleotide-binding domain like receptor
protein 3 (NLRP3)
inflammasome activation. In vitro studies,
4-hydroxyphenylacetic acid and 3-(4-hydroxyphenyl)
propionic acid, main intestinal flora metabolites of PA restrained NF-κB/NLRP3 activation. In conclusions, PA improved IR via NF-κB/NLRP3 pathway in GDM and postpartum mice, which partly through its metabolites by gut microbiome.