Maternal High-Fat Diet Impairs Pancreatic Β-Cell Development and Reduces VAMP-2 Levels in Islets of Mouse Offspring.

Maternal nutrition can influence offspring metabolism through metabolic programming, potentially leading to long-term disorders such as obesity and type 2 diabetes. However, the cellular- and tissue-level mechanisms involved in the metabolic programming, particularly regarding the endocrine pancreas, remain unclear. This study investigated the effects of maternal high-fat (HF) diet exposure on the biometric/metabolic profiles, β-cell morphometry, insulin secretion, and islet levels of the SNARE protein VAMP-2 and cytoskeletal F-actin, both critical to insulin granule exocytosis, in mouse offspring. Female C57BL6 mice were fed either a control (CON, 4.5% lipids) or a HF diet (35% lipids) during pregnancy and lactation. The offspring from both groups were evaluated at 3, 12, and 90 days of age. The offspring from HF diet-fed mothers exhibited significantly lower body weight from day 3 and increased visceral adiposity, hyperinsulinemia, glucose intolerance, and insulin resistance, associated with no significant changes in postprandial glycemia by adulthood. These alterations were accompanied by significant morphometric changes in the endocrine pancreas, including a reduction in total islet area, β-cell area, and β-cell number per islet, detectable from day 3 until adulthood. Additionally, adult islets from HF offspring showed elevated cellular F-actin labeling and reduced VAMP-2 protein levels, correlating with impaired glucose-stimulated insulin secretion in vitro. In conclusion, maternal HF diet exposure leads to metabolic disturbances and impaired β-cell function in offspring. These include reduced β-cell mass and secretory capacity, potentially due to an impaired cytoskeletal organization and insulin granule exocytosis, highlighting the long-term impact of maternal nutrition on offspring health.