Metabolic input in adult offspring of mothers without melatonin during pregnancy and lactation

Phase shifts are known to decrease night time melatonin secretion and to elicit glucose intolerance in the offspring when applied to gestating rats. In the adult rat, melatonin plays an important role in the circadian control of metabolism by timing insulin action and suppressing nocturnal gluconeogenesis. The present study addresses, therefore, the importance of maternal melatonin for the programming of the metabolic status of the offspring. We found that rats born to and breast-fed by pinealectomized mothers (PINX-P1) were glucose intolerant displaying hepatic insulin resistance and increased gluconeogenesis. No parallel changes in insulin signal transmission were detected in skeletal muscle. Pancreatic islets isolated from PINX-P1 presented impaired glucose-stimulated insulin secretion. Importantly, these alterations were detected exclusively at the end of the light phase of the light/dark cycle, indicating that PINX-P1 rats exhibit time-dependent glucose intolerance. This altered pattern of daily energy metabolism was absent in the offspring of pinealectomized mothers that received melatonin replacement during pregnancy and lactation. The present results support the novel concept that maternal melatonin is responsible for the programming of the daily pattern of energy metabolism in the offspring (AU)