The role of placental inflammasomes in linking the adverse effects of maternal obesity on fetal development

Abstract

Maternal obesity increases the risk of health complications in both the mother and the infant.In turn, the offspring of obese mothers are inclined to develop obesity, cardiovascular disease, and type 2 diabetes as adults, establishing a vicious cycle of metabolic disease.Obese mothers exhibit dyslipidemia, inflammation, and insulin resistance, factors which can negatively influence fetal development via effects on placental function.Optimal nutrient delivery to the fetus is a critical function of the placenta, and impairments in this process may modulate fetal growth and/or compromise fetal tissue development.Additionally, nutrients, in particular fatty acids, function as bioactive molecules to alter placental inflammatory status.Recent findings demonstrate increased posttranslational processing of IL-1 by an inflammatory process known as the inflammasome, in placentas of obese mothers.Inflammasome activation results in caspase-1-mediated maturation of IL-1 prior to cellular release.High circulating levels of saturated fatty acids activate and polyunsaturated fatty acids inhibit the inflammasome.In addition to its role as an immunogenic molecule, IL-1 impairs placental insulin signaling and function, thereby altering the metabolic function of the placenta.Hence placental inflammasomes may represent one of the key inflammatory mechanisms linking maternal nutrient excess to aberrant placental function and fetal development.