High-Fat Programming of β-Cell Dysfunction

Abstract

High saturated fat intake contributes to insulin resistance, β-cell dysfunction, and type 2 diabetes. Developmental programming refers to a stimulus or insult during critical periods of life which includes fetal and subsequent early neonatal life. Programming alters progeny physiology and metabolism with immediate, transient, and durable effects. Maternal nutrition and metabolic state in gestation and lactation shapes progeny development and health. However, paternal nutrition and metabolic state also shapes progeny outcomes, albeit to a lesser extent. A high saturated fat diet ingested by mothers during gestation and/or lactation presents a nutritional insult that induces diabetogenic changes in progeny physiology and metabolism. High-fat programming is induced by maternal high saturated fat intake during defined periods of gestation and/or lactation and programs the physiology and metabolism of the progeny throughout life. This more recently adopted form of developmental programming reflects society in both affluent and developing countries. High-fat programming induces adverse changes in β-cell development and function in neonatal, weanling, and adolescent progeny. These changes are characterized by compromised β-cell development and function, evident by altered expression of key factors that maintain the β-cell phenotype. High-fat programming likely prompts β-cell dysfunction and eventual type 2 diabetes. Dietary consumption, limited in high saturated fat content, particularly in fetal and early postnatal life should be adopted in progeny. Healthy parental nutrition and metabolism pre-, during, and postconception, particularly maternal, should be maintained to enhance progeny health outcomes. These early intervention strategies may prevent the onset of metabolic disease.