Caloric Restriction and Intermittent Fasting During Lactation Leads to Malnutrition, Hypothalamic Redox Imbalance and Impaired Glucose Metabolism in Male and Female Offspring of Wistar Rats

The lactation period is considered fundamental in the development of offspring in relation to their metabolism, growth and brain maturation. However, it is also during this phase that the offspring are highly susceptible to changes triggered by maternal malnutrition, which can lead to deficiencies in brain development and affect behaviour throughout life. This study investigated the effects of maternal dietary restrictions, caloric restriction (CR) and intermittent fasting (IF), during lactation on the nutritional and developmental outcomes of Wistar rat dams and offspring (males and females) into adolescence. The litters (dam and eight pups) received the following dietary conditions: control, received the lab chow (Nuvilab CR-1) ad libitum (n = 8 litters); caloric restriction (CR), received 50% of the chow (Nuvilab CR-1) consumed by the control group (n = 8 litters); intermittent fasting (IF), received lab chow (Nuvilab CR-1) ad libitum for the first 24 h, followed by a 24-h period without access to food. This procedure was repeated throughout the entire lactation period. The study measured body weight, food and water intake, serum biochemistry parameters (glucose, cholesterol, triglycerides, bilirubin, ALT/AST and creatinine) and the redox state of the hypothalamus. In relation to the dams, CR and IF groups displayed a marked weight loss during lactation. Our findings show that CR and IF led to marked undernutrition in both male and female offspring, persistent through weaning into adolescence. Both groups showed a reduction in serum glucose levels in the offspring, as well as a reduction in the activity of superoxide dismutase (SOD) in the hypothalamus. This study highlights the profound impact of maternal nutrition during lactation on offspring nutrition, suggesting that restrictive diets may compromise offspring development and metabolic health.