The absence of melatonin during gestation and its influence on glycolysis and gluconeogenesis

• Grant number: 19/05518-4
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): May 01, 2019
• Effective date (End): April 30, 2020
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: José Cipolla Neto
• Grantee: Annick Desmonts Silva
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 14/50457-0 - Melatonin and the control of energy metabolism: basic, clinical and epidemiological research, AP.TEM

Abstract

Energy metabolism is organized to deal with the needs of the body and its variations over a 24-hour period. The circulating melatonin, which is elevated at night, is synthesized by the pineal gland and acts to synchronize physiological functions, including energy metabolism. Among its functions, it is known that melatonin has action on insulin and glucose uptake; insulin is potentiated by the synthesis of melatonin as well as it is able to synchronize insulin synthesis and improve its signaling in peripheral tissues and CNS.When considered the maternal organism, studies indicate increasing serum concentrations of maternal melatonin during the gestational period in both humans and rodents, and this increase is due to stimuli of placental hormones. It is also known that the concentration of melatonin declines significantly after delivery and remains decreased in the postpartum period. Concomitantly, the fine regulation of maternal-fetal energy metabolism is observed. During this period, the maternal body assumes a physiological diabetogenic state, there is also an increase in adipose tissue mass and hyperlipidemia. These changes are essential to ensure continued delivery of nutrients to the fetus. After instillation of insulin resistance, increased lipolysis is observed. The hormones secreted by the placenta are considered the main triggers of maternal physiological reprogramming. In the first two trimesters of pregnancy, the maternal body stores fat that will be used in the last trimester of pregnancy. The constant increase in nutrient availability is a consequence of increased insulin resistance in the mother. Glycolysis and gluconeogenesis also present alterations due to the aforementioned modifications. Thus, in view of changes in both glucose metabolism and lipid metabolism and the important metabolic role of melatonin in this scenario, the objective of the present study will be to investigate the pathways of glycolysis and gluconeogenesis under conditions of maternal hypomelatoninemia and consequent changes in pregnant rats. For this, Wistar rats, divided into four experimental groups: 1) pregnant rats, 2) pinealectomized pregnant rats, 3) pinealectomized pregnant rats with fixed dose melatonin replacement, and 4) pinealectomized pregnant rats with melatonin replacement at variable doses . The animals will undergo GTT and ITT tests and hormonal dosages on the 7th and 14th days of pregnancy and then euthanized after completing 21 days of gestation two hours before and two hours after the beginning of the dark period of the vivarium (ZTs 10 and 14 ). The project will have 2 sets of animals, being: set 1 euthanized in G21 in ZT10, set 2 euthanized in G21 in ZT14, blood and liver will be collected. The liver tissue will be submitted to the following tests: (I) colorimetry for analysis of liver function markers, (II) kinetics of the key enzymes involved in glycolysis and gluconeogenesis, and (III) quantification of the protein content of the routes involved by Western blotting. Through the results obtained in this project, it is expected to understand the essential role that melatonin has during the gestational period, as well as to identify the influence of the same on the lipid metabolism and its function in the maintenance of the gestational period.