Prenatal Choline Supplement in a Maternal Obesity Model Modulates Offspring Hepatic Lipidomes

Abstract

Maternal obesity during pregnancy adversely impacts offspring health, predisposing them to chronic metabolic diseases characterized by insulin resistance, dysregulated macronutrient metabolism, and lipid overload, such as metabolic-associated fatty liver disease (MAFLD). Choline is a semi-essential nutrient involved in lipid and one-carbon metabolism that is compromised during MAFLD progression. Here, we investigated under high-fat (HF) obesogenic feeding how maternal choline supplementation (CS) influenced the hepatic lipidome of mouse offspring. Our results demonstrate that maternal HF+CS increased relative abundance of a subclass of phospholipids called plasmalogens in the offspring liver at both embryonic day 17.5 and after 6 weeks of postnatal HF feeding. Consistent with the role of plasmalogens as sacrificial antioxidants, HF+CS embryos were presumably protected with lower oxidative stress. After postnatal HF feeding, the maternal HF+CS male offspring also had higher relative abundance of both sphingomyelin d42:2 and its side chain, nervonic acid (FA 24:1). Nervonic acid is exclusively metabolized in the peroxisome and is tied to plasmalogen synthesis. Altogether, this study demonstrates that under the influence of obesogenic diet, maternal CS modulates the fetal and postnatal hepatic lipidome of male offspring, favoring plasmalogen synthesis, an antioxidative response that may protect the mouse liver from damages due to HF feeding.