Prenatal stress promotes insulin resistance without inflammation or obesity in C57BL/6J male mice

Abstract

During gestation, stress exposure increases the risk of developing cognitive and physiological alterations in either the long or short term. Among them, metabolic alterations have been described. Adipose tissue is responsible for the secretion of several factors involved in controlling body weight and energy expenditure, the regulation of insulin sensitivity, and the development of inflammation, among others. Moreover, the liver regulates glucose homeostasis and lipid metabolism, playing an essential role in developing insulin resistance. In this work, we analyzed if prenatal stress leads to alterations in metabolism and the relationship between these alterations and gene expression in the adipose tissue and the liver. Prenatal stress-exposed animals developed disturbances in the glucose and insulin response curve, showing in both tests higher glycemia than the control group. However, they did not exhibit increased body weight. At the same time, in the adipose tissue, we observed an increase in mRNA expression of Leptin and Resistin and a decrease in Adiponectin. In the liver, we observed a lower mRNA expression of several genes involved in glucose metabolism and fatty acid oxidation, such as Sirt1, Pgc1α, Pparα, among others. In both tissues, we observed a lower expression of inflammatory genes. These results suggest that prenatal stress exposure produces insulin resistance at both physiological and molecular levels without pro-inflammatory signaling or obesity.

Keywords: Prenatal stress; adipose tissue; fetal programming; gene expression; insulin resistance; liver.