Ferulic acid protects rat offspring from maternal high-fat, high-fructose diet-induced toxicity and developmental retardation through a direct effect on pancreatic islets.

Maternal obesity predisposes offspring to type 2 diabetes (T2D) through a direct chronic effect of lipids on pancreatic β-cell neogenesis. β-cells produce FABP3 to bind and metabolize fatty acids. Ferulic acid (FA) is a natural product that may inhibit fatty acids' binding to FABP3, preventing their toxicity. It is aimed to evaluate the consequences of maternal feeding on high-fat, high fructose diet (HFFD) and the role of FA on the offspring. Four-week-old female rats were fed HFFD for 9 weeks prior to and throughout gestation and lactation to develop T2D. A group of them received 50 mg/kg FA daily. Offspring were sampled on gestational day 18 (GD18), and postnatal days (PND) 3 and 30. HFFD increased offspring's blood glucose, insulin, Homa-IR, HbA1c, triglycerides, cholesterol, intrahepatic and intra-insular lipid droplets. The mechanism of islet inflammation and apoptosis, detected by Il-1b and cleaved caspase3, involved the nuclear translocation of NFκB p65. Maternal HFFD caused developmental retardations in offspring's ovaries, testes, kidney and liver. Coupling FA treatment with the maternal HFFD maintained normoglycemia, lipidemia, and healthy islets, and prevented developmental retardations. FA administration to T2D mothers revealed positive effects on the offspring that is related to its direct protective effect on pancreatic β-cells.