# Maternal AGE Precursors During Lactation Alters Offspring Glycemic Homeostasis Early in Life

## TL;DR

Exposure to a dietary toxin during breastfeeding in rats affects offspring's blood sugar control and pancreatic function early in life.

## Contribution

This study reveals that maternal intake of methylglyoxal during lactation impairs offspring's early metabolic health and pancreatic function.

## Key findings

- MG offspring had reduced bodyweight and fat mass at weaning.
- MG offspring showed impaired glucose tolerance and lower insulin production.
- MG offspring pancreas exhibited increased stress markers and reduced function.

## Abstract

Our research focused on how maternal exposure to dietary toxins during lactation influences the offspring’s physiological development. Breastfeeding Wistar rats were exposed to a compound called methylglyoxal (MG), a precursor to harmful substances known as advanced glycation end-products. Our data showed that the offspring from lactating MG faced difficulties in managing blood sugar levels, linked to lower insulin production, which is critical for maintaining proper glycemic control. Also, MG offspring pancreas, the only endogenous insulin source, showed signs of greater stress and reduced function in early life. These results reinforce the evidence that what a mother consumes while breastfeeding can significantly impact her child’s metabolic health, potentially increasing the risk of noncommunicable chronic diseases like diabetes in the future.

Background: Advanced glycation end-products (AGEs) are linked to the development of oxidative stress, insulin resistance, and impaired insulin secretion. Adverse early life conditions, such as exposure to AGEs and their precursors, may lead offspring to the development of metabolic dysfunction in adulthood. Nonetheless, the early impact in offspring metabolism by maternal intake of AGEs precursors during lactation is not known. Objective: Investigate early life metabolism of the offspring whose breastfeeding dams were orally exposed to AGEs precursor. Methods: Breastfeeding Wistar rats were daily treated with the glycation precursor methylglyoxal (MG—60 mg/kg of bodyweight) by gavage or saline 0.9% control (CO) until weaning. In vivo glycemic homeostasis in male offspring was assessed, followed by euthanasia for tissue sample collection for ex vivo assessments. Results: At weaning, MG offspring presented decreased bodyweight (p < 0.05), perigonadal (p < 0.01) and retroperitoneal (p < 0.01) fat. MG offspring presented decreased glucose tolerance (p < 0.05), lower basal insulinemia (p < 0.001), reduced high-glucose static insulin secretion (p < 0.05), and reduced pancreatic islet area (p < 0.05). Accordingly, MG offspring pancreas showed lower GSH and SOD activity (p < 0.05; p < 0.001, respectively) and increased MPO (p < 0.05) activity. Conclusions: The consumption of AGE precursors by breastfeeding dams impaired offspring pancreatic function and glycemic homeostasis early in life.