Fermented Lentinus edodes improves insulin sensitivity in dam and offspring mice via activation of the hepatic PI3K/AKT signaling pathway

Abstract Overnutrition during before and pregnancy can cause maternal obesity and raise the risk of maternal metabolic diseases during pregnancy, and in offspring. Lentinus edodes may prevent or reduce obesity. This study aimed to to assess Lentinus edodes fermented products effects on insulin sensitivity, glucose and lipid metabolism in maternal and offspring, and explore its action mechanism. A model of overnutrition during pregnancy and lactation was developed using a 60 % kcal high-fat diet in C57BL6/J female mice. Fermented Lentinus edodes (FLE) was added to the diet at concentrations of 1 %, 3 %, and 5 %. The results demonstrated that FLE to the gestation diet significantly reduced serum insulin levels and homeostatic model assessment for insulin resistance (HOMA-IR) in pregnant mice. FLE can regulate maternal lipid metabolism and reduce fat deposition. Meanwhile, the hepatic phosphoinositide-3-kinase-protein kinase (PI3K/AKT) signaling pathway was significantly activated in the maternal mice. There is a significant negative correlation between maternal FLE supplementation doses and offspring body fat percentage and visceral fat content. Furthermore, FLE supplementation significantly increased offspring weaning litter weight, significantly reduced fasting glucose level, serum insulin level, HOMA-IR and serum glucose level, significantly activated liver PI3K/AKT signaling pathway in offspring, and upregulated the expression of liver lipolytic genes adipose triglyceride lipase, hormone-sensitive lipase and carnitine palmitoyltransferase 1 mRNA. Overall, FLE supplementation can regulate maternal lipid metabolism and reduce fat deposition during pregnancy and lactation, and it may improve insulin sensitivity in pregnant mothers and offspring at weaning through activation of the PI3K/AKT signaling pathway.