Transgenerational effects of maternal circadian melatonin deficiency and melatonin replacement in rats during pregnancy and lactation on the energy metabolism and thermoregulation in the offspring subjected to a high-fat diet

Abstract

Pineal melatonin participates in the control of numerous biological functions through its immediate effects, which result from its high presence in the systemic circulation during the dark phase of the circadian cycle or, through its prolonged effects, when its level is extremely low during the light phase. At pregnancy, maternal melatonin signals the external photoperiod to the fetus, highlighting its importance not only in synchronizing rhythms, but also in preparing the fetus to adapt the external environments. The fetus and newborns are exclusively dependent on maternal melatonin since their pineal melatonin production only occurs weeks after birth. Thus, maternal hypomelatoninemia stands out as an important factor capable of modulating the physiological systems of their descendants, demonstrating its transgenerational capacity. The present study evaluated the transgenerational influence of maternal melatonin deficiency and replacement during pregnancy on morphometric parameters, thermoregulation and energy metabolism of the offspring submitted to the normal and high-fat diets, respectively. For this, nulliparous Wistar rats at an age of 8 weeks were used and randomized into three groups: CTL (pregnant rats), PINX (pinealectomized pregnant rats), PINX + MEL (pinealectomized pregnant rats submitted to melatonin replacement). After birth, the pups were divided into three groups: (C) pups from control mothers, (P) pups from PINX mothers and (PM) pups from PINX + MEL mothers. One week after weaning, part of the animals was fed a high-fat diet (DH) and rest of them were fed a normal diet (ND) for 12 weeks. Subsequently, the animals were euthanized at ZTs 6 and 18. The results showed that maternal melatonin deficiency disrupted the energy metabolism of the offspring and melatonin replacement normalized the energy metabolism in the offspring submitted to the high-fat diet, enabling them to make functional adaptations such as reduced food consumption and greater thermoregulatory capacity, resulting in reduction in body weight gain white adipose tissue mass.