Effects of Zinc Deficiency and Supplementation on Leptin and Leptin Receptor Expression in Pregnant Mice

Abstract

Leptin is an adipose-derived hormone that primarily regulates energy balance in response to nutrition. Human placental cells produce leptin, whereas murine placental cells produce soluble leptin receptors (Ob-R). However, the roles of these proteins during pregnancy have not been elucidated completely. As an essential metal, zinc (Zn) is central to insulin biosynthesis and energy metabolism. In the present study, the effects of Zn deficiency and supplementation on maternal plasma leptin and soluble Ob-R regulation in pregnant mice placentas were examined using enzyme-linked immunosorbent assay, reverse transcriptionpolymerase chain reaction, and Western blotting. Nutritional Zn deficiency significantly reduced plasma insulin concentrations and fetal and placental weights in pregnant mice. Plasma leptin concentrations in pregnant mice also increased 20-to 40-fold compared with those in non-pregnant mice. Although dietary Zn deficiency and supplementation did not affect plasma leptin concentrations in non-pregnant mice, Zndeficient pregnant mice had significantly reduced plasma leptin concentrations and adipose leptin mRNA expression. In contrast, Zn-supplemented pregnant mice had increased plasma leptin concentrations without increased adipose leptin mRNA expression. Placental soluble Ob-R mRNA expression also decreased in Zndeficient mice and tended to increase in Zn-supplemented mice. These results indicate that Zn influences plasma leptin concentrations by modulating mRNA expression of soluble Ob-R in the placenta, and leptin in visceral fat during pregnancy. These data suggest that both adipose and placenta-derived leptin system are involved in the regulation of energy metabolism during fetal growth. Key words leptin; leptin receptor; dietary zinc; pregnancy; placentaLeptin is a 16-kDa protein hormone encoded by lep and is mainly produced in adipose tissues. Initial studies indicated that it regulates body weight by suppressing appetite and stimulating energy consumption via the hypothalamic leptin receptor (Ob-R).1,2) In addition to its known role in energy metabolism, pleiotropic effects of leptin have been identified, involving modulation of thermogenesis, homeostasis, hematopoiesis, angiogenesis, neuroendocrine, and immune functions. Moreover, leptin regulates ovarian function, oocyte maturation, and implantation.3,4) Recently, significantly elevated plasma leptin concentrations were found in pregnant women, with considerable leptin secretion from the placenta in comparison with that observed in non-pregnant women. 5)In the second and third trimesters, plasma leptin concentrations further increased in comparison with that observed in the first trimester and returned to normal after expulsion of placenta, suggesting that the placenta is the major source of leptin during pregnancy. 5) Leptin is not produced in mouse placentas, although plasma leptin concentrations are also elevated during pregnancy, and high placental production of soluble Ob-R has been demonstrated in mice. It was reported that secretions ...

RETRACTED ARTICLE: The Effect of Zinc Supplementation on Expressed Levels of Peroxisome Proliferator-Activated Receptor Gamma and Glucose Transporter Type 1 Genes in Newborns of Women with Gestational Diabetes Mellitus

“…In a study by Ueda et al [11], it was seen that at day 17 of gestation, the expression of placental GLUT1 mRNA did not affect following the supplementation with zinc, but that observed in zinc-deficient mice significantly decreased to 70 % of that observed in control mice. However, zinc element did not influence expressed levels of GLUT1 in C6 rat glioma and GP8 rat brain endothelial cells [25].…”

“…In addition, placental glucose transporter type 1 (GLUT-1) plays an important function in transporting glucose from mother to fetus [10]. In a study by Ueda et al [11] was seen that expression levels of placental GLUT-1 mRNA in zinc-deficient pregnant mice was significantly decreased than that observed in control pregnant mice, whereas it unchanged in zincsupplemented pregnant mice.…”

Placental adaptations to micronutrient dysregulation in the programming of chronic disease

“…Zinc deficient mice have reduced placental glucose transporter 1 (GLUT1) expression as well as reduced placental and foetal weights . Selenium supplementation in GDM women is known to improve maternal glucose metabolism .…”

“…Zinc deficient mice have reduced placental glucose transporter 1 (GLUT1) expression as well as reduced placental and foetal weights. 64 Selenium supplementation in GDM women is known to improve maternal glucose metabolism. 65 Given the importance of correct hormone signalling during pregnancy, it is also important to understand how micronutrients affect placental hormone metabolism and signalling.…”

Effects of Zinc Deficiency in Male Mice on Glucose Metabolism of Male Offspring

“…8) Zinc deficiency is associated with a variety of diseases, and could cause systemic health problems, including growth and development, neurological dysfunction, reproductive and immune system damage etc. 9,10) Marginal zinc deficiency refers to zinc deficiency with zinc ion level reduced in blood circulation in the body, but no signs of skin injury, hair loss and other signs, 11) which is the most common type of zinc deficiency in population, especially in children.…”