Perinatal consumption of a thermally processed diet alters feeding behavior and has sex-dependent effects upon metabolism in later life in mice.

Intense thermal processing of food, industrial or domestic, alters the food matrix leading to degradation of thermolabile vitamins such as thiamine, and to the formation of color and aroma compounds via the Maillard reaction which influence palatability and consumer preference. In the literature, baked diets are used to mimic industrial food processing and to study protein glycation in animal models; however, the relationships between food matrix transformation, metabolic outcomes, and food preference remain poorly understood. We hypothesized that perinatal exposure to a thermally processed food may disrupt metabolism and influence food intake. We quantified nutritional losses and Maillard reaction products (MRP) and assessed food preference and energy metabolism in 8-week-old, male and female C57BL/6 mice exposed perinatally to a standard (STD) or a baked (BKD) diet under controlled conditions. Compared with a STD diet, BKD showed lower lysine (1.2-fold) and thiamine (∼7-fold) content, alongside higher levels of carboxymethyllysine (4.5-fold), hydroxymethylfurfural (3-5-fold), and 2-furanmethanol (up to 9-fold). Although intake did not differ during compulsory feeding, mice preferred STD, as indicated by a decrease in BKD intake. Male mice exhibited reductions in lean mass and increased plasma urea, consistent with altered protein metabolism. Females displayed increased leptin, TNFα, and leptin receptor expression, whereas males showed reduced Resistin and increased GSK3β expression. No major hypothalamic gene expression shifts were detected. Early-life exposure to a baked diet induced sex-specific metabolic alterations associated with reduced consumption of MRP-rich foods in adulthood, likely driven by peripheral metabolic signals rather than central hypothalamic regulation.