Impact of maternal undernutrition on hypothalamo-pituitary-adrenal axis and adipocyte functions in male rat offspring

Malnutrition induces profound deleterious effects on several metabolic and neuroendocrine functions. In the present study, we examined the impact of m aternal food restriction, during gestation and lactation, on the metabolic- neuroendocrine function of their male offspring at 21 and 60 d of age, Well -nourished (WN) and undernourished (UN) pregnant rats were used, during ges tation and lactation, until pups were weaned. Twenty-one-day-old WN and UN male pups were studied in basal and postinsulin conditions. Additional grou ps of weaned (WN and UN) male rats were fed either ad libitum (WN-WN and UN -WN) or in a restricted fashion (WN-UN and UN-UN) until experimentation at age 60 d. Body weights of mothers and their male offspring were monitored. Basal and postinsulin plasma concentrations of several metabolic fuels were evaluated. Our results indicate that 21-d-old UN male rats exhibited (vs t heir WN counterparts), decreased body weights, similar basal and postinsuli n glycemia, similar basal plasma adrenocorticotropic hormone (ACTH) and cor ticosterone levels but diminished ACTH response to insulin treatment, and b asal hypoleptinemia and significant insulin-induced leptin release. Finally , at 60 d of age, long-term UN (WN-UN and UN-UN) rats showed lower plasma ( basal and postinsulin) glucose, and basal triglyceride levels than their co unterparts (WN-WN and UN-WN). Sixty-day-old rats submitted to either food r estriction protocol also showed a reduced hypothalamo-pituitary-adrenal axi s response to insulin-induced hypoglycemia and basal hypoleptinemia, in spi te of restoration of normal body weights, These results further indicate a clear metabolic-neuroendocrine dysfunction in male pups of UN mothers, with the abnormality partially present at weaning and deteriorated by adulthood , even after the recovery of normal body weight, Our study strongly support s the importance of the irreversibility of a deleterious allostatic state r esulting from fetal and early postnatal undernutrition.