Protein Restriction During Pregnancy and Lactation Triggers Steatohepatitis and Adrenal Disorders in Rat Dams: Insights into Maternal Metabolic Health

Abstract

Background: The Developmental Origins of Health and Disease (DOHaD) concept is strongly supported by epidemiological and experimental data demonstrating that exposure to adverse conditions early in life can impact offspring health. Despite numerous studies showing the early and long-term impacts of maternal malnutrition on offspring, little research has been conducted on its effects on mothers.

Methods: We investigated the effects of protein restriction (6 %) during gestation and lactation on the metabolism, as well as the structural and molecular parameters of the livers and adrenals of dams.

Results: A decrease in food and water consumption was observed in gestational and lactational low-protein (GLLP) mothers during lactation, in addition to systemic changes with a decrease in aspartate aminotransferase (AST) and an increase in creatinine. The adrenal glands of GLLP mothers demonstrated cortical vacuolization and reduced collagen deposition. The liver of GLLP mothers showed a decrease in collagen and an increase in fibrotic areas, macro- and microvesicular steatosis, and hypertrophy, indicating nonalcoholic steatohepatitis (NASH). We observed decreased gene expression of Cyp11b2 and increased expression in Sts and Por in the adrenals of the GLLP group. In the liver, there was a decrease in Ppar g and Hsd3b1, in addition to increased gene expression of Pdh1, Cs, and Pklr in the GLLP group.

Conclusions: Maternal protein restriction (MPR) leads to systemic and structural disorders on the adrenal-liver axis, affecting important molecular processes that indicate hepatic and adrenal stress, as well as disorders in energy metabolism. This could potentially affect the fetal and postnatal health of the offspring, increasing the risk of diseases.

Keywords: Adrenal glands; Diet; Dohad; Liver; Maternal malnutrition; Metabolic programming.