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Study of the Ghrelin/LEAP-2 Ratio in Humans and Rats during Different Phases of Pregnancy

2022; Multidisciplinary Digital Publishing Institute; Volume: 23; Issue: 17 Linguagem: Inglês

10.3390/ijms23179514

1661-6596

María Fernanda Garcés, Julieth Daniela Buell‐Acosta, Edith Ángel‐Müller, Arturo José Parada Baños, Jaidy Acosta-Alvarez, Harold Felipe Saavedra-López, Roberto Franco-Vega, Luis Miguel Maldonado‐Acosta, Franklin Escobar-Córdoba, Keydy Vásquez-Romero, Ezequiel Lacunza, Sofía Alexandra Caminos-Cepeda, Rubén Nogueiras, Carlos Diéguez, Ariel Iván Ruíz‐Parra, Jorge Eduardo Caminos,

Adipokines, Inflammation, and Metabolic Diseases

The Liver-Expressed Antimicrobial Peptide 2 (LEAP-2) has emerged as an endogenous GHS-R antagonist and blunts the orexigenic action of ghrelin. This study aimed to determine the Ghrelin/LEAP-2 ratio in humans and rats during pregnancy. In humans, we conducted a nested case-control study within an observational prospective cohort. Healthy and mild preeclamptic pregnant women were studied at each trimester of gestation and three months postpartum. In addition, a group of non-pregnant women was studied into the follicular and luteal phases of the menstrual cycle. Furthermore, Ghrelin/LEAP-2 ratio was investigated in non-pregnant rats and at different periods of rat pregnancy. Human and rat serum ghrelin and LEAP-2 levels were determined using the commercially available ELISA kits. The Ghrelin/LEAP-2 ratio peak around the second trimester of gestation in healthy pregnant women (p < 0.05). Additionally, there were no statistically significant differences in Ghrelin/LEAP-2 ratio between healthy and preeclamptic pregnant women at each trimester of gestation (p > 0.05). The Ghrelin/LEAP-2 ratio in pregnant rat reached the peak around mid-gestation with a similar pattern to the human pregnancy. LEAP-2 was visualized by immunohistochemistry in human term placenta and rat placentas on days 12, 16 and 21 of pregnancy. In conclusion, this study provides the first evidence of a Ghrelin/LEAP-2 ratio peak around the half-way point of pregnancy onwards during human and rat pregnancy, and it might be associated with increased rates of weight gain during pregnancy. Thus, this study suggests that LEAP-2 and Ghrelin/LEAP-2 ratio might play an important role in maternal physiology adaptation of weight gain during pregnancy.