Expression of nutrient transporters in placentas affected by gestational diabetes: role of leptin

Front Endocrinol (Lausanne). 2023 Jul 11:14:1172831. doi: 10.3389/fendo.2023.1172831. eCollection 2023.

Abstract

Gestational diabetes mellitus (GDM) is the most frequent pathophysiological state of pregnancy, which in many cases produces fetuses with macrosomia, requiring increased nutrient transport in the placenta. Recent studies by our group have demonstrated that leptin is a key hormone in placental physiology, and its expression is increased in placentas affected by GDM. However, the effect of leptin on placental nutrient transport, such as transport of glucose, amino acids, and lipids, is not fully understood. Thus, we aimed to review literature on the leptin effect involved in placental nutrient transport as well as activated leptin signaling pathways involved in the expression of placental transporters, which may contribute to an increase in placental nutrient transport in human pregnancies complicated by GDM. Leptin appears to be a relevant key hormone that regulates placental transport, and this regulation is altered in pathophysiological conditions such as gestational diabetes. Adaptations in the placental capacity to transport glucose, amino acids, and lipids may underlie both under- or overgrowth of the fetus when maternal nutrient and hormone levels are altered due to changes in maternal nutrition or metabolic disease. Implementing new strategies to modulate placental transport may improve maternal health and prove effective in normalizing fetal growth in cases of intrauterine growth restriction and fetal overgrowth. However, further studies are needed to confirm this hypothesis.

Keywords: amino acids; fetal macrosomia; gestational diabetes mellitus; glucose; leptin; lipids; nutrient transporters; placental transport.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acids / metabolism
  • Diabetes, Gestational* / metabolism
  • Female
  • Fetal Macrosomia / etiology
  • Glucose / metabolism
  • Humans
  • Leptin / metabolism
  • Lipids
  • Membrane Transport Proteins / metabolism
  • Nutrients
  • Placenta* / metabolism
  • Pregnancy

Substances

  • Amino Acids
  • Glucose
  • Leptin
  • Lipids
  • Membrane Transport Proteins
  • LEP protein, human

Grants and funding

We acknowledge the financial support of the Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación, Spain, Grant n° PI19/01741 funded in part by FEDER Funds, to VS-M and AP-P; and the Consejería de Conocimiento e Investigación, Junta de Andalucía, Spain, Grant n° P20_01253, to VS-M.