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.

Prenatal Choline Supplementation Improves Glucose Tolerance and Reduces Liver Fat Accumulation in Mouse Offspring Exposed to Ethanol during the Prenatal and Postnatal Periods

“…In addition, the male offspring demonstrated altered Ppara and Ldlr expression with the combined effect of prenatal and postnatal AE, while in female offspring, postnatal AE alone was sufficient to downregulate Ldlr expression. Overall, it seems that male offspring or those with a higher AE dosage were more susceptible to prenatal AE and responsive to CS [31,44,47]. In a prior study of 4 g/kg prenatal AE only, female offspring were found to have a greater reduction in SR-B1 and CYP7A1 cholesterol metabolic gene expression and thus potentially more susceptible to cholesterol dysregulation [9].…”

Fetal sex differences in placental LCPUFA ether and plasmalogen phosphatidylethanolamine and phosphatidylcholine contents in pregnancies complicated by obesity

“…This fatty acid is exclusively catabolized in the peroxisome and its breakdown is considered a source for alkyl groups in plasmalogen synthesis [ 55 ]. Inversely, a supplementation of choline to pregnant mice fed with a high-fat diet increases the relative abundance of hepatic plasmalogen and sphingomyelin d42:2 (SM d18:1_24:1, containing nervonic acid) in fetus at 17.5 day of gestation and after 6 weeks postnatal in male offspring, indicating an antioxidative response to protect the mouse liver from damages due to high-fat feeding [ 56 ]. Another study has shown that choline supplementation increased the incorporation of DHA into choline-containing phospholipids in a mouse model of maternal obesity [ 57 ].…”

Maternal Obesity and Kawasaki Disease-like Vasculitis: A New Perspective on Cardiovascular Injury and Inflammatory Response in Offspring Male Mice

“…Evidence from epidemiological, clinical, and animal studies have demonstrated that obesity affects not only maternal health, but also the long-term outcomes of offspring, with increased risk of obesity and cardiovascular disease (CVD) later in life [2][3][4]. Although the exact mechanisms of the transgenerational effect of maternal obesity remains unclear, fetal programming has been suggested to play a pivotal role in this process [5][6][7]. Human studies have provided evidence for the mechanisms underlying the link between maternal obesity and offspring cardiovascular disease.…”