Maternal monosodium glutamate exposure disrupts leptin and insulin signaling in the hypothalamus, activating NF-κB and mTOR inflammatory pathways, contributing to metabolic dysfunction in male offspring.

Abstract

Maternal nutrition during critical developmental windows is increasingly recognised as a key determinant of offspring health, a concept central to the developmental origins of health and disease paradigm. Monosodium glutamate (MSG), a common food additive and neuroendocrine stimulant, warrants investigation in this context. The impact of maternal MSG exposure (120 mg/kg) during gestation and/or lactation on metabolic programming in first-generation male rat offspring. Metabolic, hormonal, and molecular parameters in pups following maternal MSG administration, body weight, food intake, adiposity, glucose homeostasis (insulin sensitivity and resistance), lipid profiles, oxidative stress markers, and inflammatory mediators were measured. Furthermore, we analyzed microRNA expression profiles in relevant tissues. Maternal MSG exposure resulted in significant metabolic perturbations in offspring. Key findings included a reduced survival index, impaired glucose homeostasis (manifesting as decreased insulin sensitivity and increased insulin resistance), increased body weight, and elevated adiposity. We observed elevated oxidative stress, dyslipidemia, altered lipid peroxidation, and hormonal imbalances. Quantitative PCR analysis revealed altered expression of metabolic and inflammatory genes in both adipocytes and the hypothalamus. MicroRNA expression analysis identified significant alterations in miR-27a, miR-34a, miR-335, and miR-30a, suggesting potential regulatory roles in adipogenesis and metabolic control. Maternal MSG exposure during gestation and lactation induces profound and adverse metabolic effects in male offspring. The observed alterations in metabolic indices suggest an increased risk of metabolic disease later in life. This study underscores the critical importance of maternal nutrition during sensitive developmental periods and has implications for public health recommendations and nutritional guidelines (Graphical abstract).