Long-term programming of liver lipid metabolism in offspring of dams fed western diet from the pregestational period and its potential reversal by vitamin A supplementation during lactation

Abstract

[eng] It is known that during critical stages of life, the organism is characterized by high plasticity in front of changes to adapt and achieve survival. These, either beneficial or unbeneficial changes, might be influenced by diet and environmental factors, mainly during pregnancy and lactation, establishing metabolism patterns and alterations that might provoke certain outcomes in the adulthood. In this pilot study, we aim to prove that a maternal western diet (WD) causes such changes in the hepatic lipid metabolism of the offspring and to explore whether vitamin A forms, namely β-carotene (BC) and retinyl palmitate (RP), supplementation during lactation might reverse these adverse outcomes. C57BL/6 mice dams were fed a WD during gestation and lactation and their offspring were supplemented with different forms of vitamin A during lactation -BC and RP- until day 21. In adult life, they continued feeding on a WD, too. We observed a WD-induced upregulation of genes involved in both de novo lipogenesis and fatty acid oxidation (FAO), and downregulation of the cholesterol biosynthesis pathway, suggesting a metabolic response due to lipid accumulation generated by a highfat and high sucrose diet, and satiety caused by the elevated cholesterol content of the diet. In addition to that, we found a possible reverse of the WD-induced hepatic lipid alterations by RP supplementation during lactation, suggesting a nutrigenetic impact. RP attenuated adipose index, glycemic levels, and insulin sensitivity, as well as gene expression (Plin2, Srepbf2). This potent effect by RP might have a greater impact considering the establishment of a more normalized response, even after the maintenance of WD during adulthood.