Embryonic and Neonatal Exposure to High-Fat Diet Disrupted Pancreatic Oxidative and Endoplasmic Reticulum Homeostasis Alongside Islet Insulin Output in Pubertal Rats

High-fat diet (HFD), adversely affects redox and/or endoplasmic reticulum (ER) stress status in pancreatic islets and disrupts glucose homeostasis. Additionally, maternal HFD can cause metabolic disorders in offspring at an older age. Hence, we studied the impact of HFD during pregnancy and lactation on oxidative stress and ER stress indices along with the quantity of insulin produced and released by the pancreatic islets in pubertal rat offspring. For this, pregnant rats were allocated into two groups fed either with the standard (S) or high-fat (HF) diet during pregnancy and lactation. After weaning, male pups from each group consumed standard diet until puberty. At puberty, the offspring plasma levels of glucose, insulin, leptin and corticosterone were assessed along with their ability to handle a glucose load. Finally, offspring pancreases were evaluated for oxidative and ER stress biomarkers as well as for isolated islets’ glucose-induced insulin release (GIR) and content. The data obtained showed that the offspring from the HF group had elevated intra-abdominal fat mass and plasma corticosterone and leptin levels, but reduced body weight. HFD also increased pancreatic MDA level, whereas it decreased catalase activity. In the HF group, protein levels of pancreatic immunoglobulin heavy-chain binding protein (BIP), CCAAT/enhancer-binding protein homologous protein (CHOP), and wolframin ER transmembrane glycoprotein (WFS1) were increased. However, glucose tolerance and homeostatic model assessment for insulin resistance (HOMA-IR) index in the HF offspring did not change. The isolated pancreatic islets of the HF group showed disturbed glucose-induced insulin release (GIR) with unchanged insulin content. It can be concluded that maternal consumption of HFD leads to a rise in pancreatic markers of oxidative and ER stress in pubertal offspring and the increased pancreatic Wolfram syndrome 1 (WFS1) level could be a crucial factor in preserving glucose homeostasis.