Maternal butyrate administration ameliorates fetal fatty liver and maternal metabolic alterations related to maternal obesity.

Obesity negatively impacts maternal and fetal metabolism, leading to the programming of metabolic disturbances in the offspring. We have previously reported numerous maternal, fetal and offspring alterations in a rat model of obesity. In this study, we administered butyrate-a short-chain fatty acid derived from gut microbiota metabolism-to obese mother rats during pregnancy and lactation in an attempt to improve maternal health and prevent the fetal features associated with the programming of fatty liver disease. The initial experimental study design comprised female Albino-Wistar rats assigned to either a control diet (C group) or a high-fat diet (FD group) to induce obesity, before being paired with control males. Pregnant rats received either butyrate (CB or FDB) or water as a vehicle (C or FD) during gestation and were euthanized at day 21 of pregnancy. The second experimental design comprised C, FD, and FDB rats that gave birth and breastfed their pups, with mothers being euthanized at the conclusion of the lactation period. At term gestation, rats with obesity exhibited increased adiposity, hepatic lipid accumulation, triglyceridemia, and circulating IL-1β. Their fetuses displayed increased body weight, liver lipid over-accumulation, and altered mRNA levels of genes involved in liver damage. Notably, butyrate administration decreased maternal circulating levels of triglycerides and IL-1β, and prevented fetal overweight status and hepatic lipid accumulation at term gestation. Importantly, butyrate exerted no effect on control rats or their fetuses. Moreover, butyrate administration ameliorated features of fatty liver disease in overweight rats at the end of lactation, further demonstrating its beneficial effects on both mothers and fetuses in this rat model of obesity.