Obesity is an important risk factor for the development of pregnancy complications. We investigated the effects of pregestational overweight and obesity on maternal lipidome during pregnancy and on newborns’ characteristics. The study encompassed 131 pregnant women, 99 with pre-pregnancy body mass index (BMI) < 25 kg/m² and 32 with BMI ≥ 25 kg/m². Maternal lipid status parameters, plasma markers of cholesterol synthesis and absorption and sphingolipids were determined in each trimester. Data on neonatal height, weight and APGAR scores were assessed. The results showed a higher prevalence (p < 0.05) of pregnancy and childbirth complications among the participants with elevated pregestational BMI. Levels of total cholesterol, HDL-cholesterol (p < 0.05) and LDL-cholesterol (p < 0.01) were significantly lower, and concentrations of triglycerides were higher (p < 0.05) in women with increased pre-gestational BMI. Lower concentrations of the cholesterol synthesis marker, desmosterol, in the 2nd trimester (p < 0.01) and the cholesterol absorption marker, campesterol, in each trimester (p < 0.01, p < 0.05, p < 0.01, respectively) were also found in this group. Markers of maternal cholesterol synthesis were in positive correlation with neonatal APGAR scores in the group of mothers with healthy pre-pregnancy weight but in negative correlation in the overweight/obese group. Our results indicate that gestational adaptations of maternal lipidome depend on her pregestational nutritional status and that such changes may affect neonatal outcomes.

Excessive gestational weight gain may be associated with unfavorable pregnancy outcomes. We explored the impact of excessive weight gain on components of HDL metabolism in maternal plasma: sterol composition of HDL particles, distribution of HDL subclasses and SCARB1, ABCA1 and ABCG1 genes expressions and their associations with newborns’ characteristics. The study included 124 pregnant women, 58 with recommended and 66 with excessive weight gain. Concentrations of cholesterol synthesis marker, desmosterol, within HDL increased during pregnancy in both groups of participants. In women with excessive weight gain, levels of cholesterol absorption marker, campesterol, within HDL were significantly lower in the 3^rd trimester compared to the 1^st and 2^nd trimesters. Relative proportions of large HDL 2b subclasses increased during pregnancy in women with recommended weight gain. Women with high pre-pregnancy BMI and excessive gestational weight gain had the lowest levels of β-sitosterol within HDL and the highest relative proportions of HDL 3a and HDL 3b subclasses in the 2^nd trimester. Large HDL 2b particles were in positive correlation, while smaller HDL 3 subclasses and SCARB1 gene expressions were in negative correlation with APGAR scores. In conclusion, excessive weight gain could contribute to altered metabolism of HDL, and subsequently to poorer neonatal outcomes.

Cholesterol accumulation plays a significant role in the pathogenesis of metabolic-dysfunction-associated steatotic liver disease (MASLD), yet changes in cholesterol homeostasis in MASLD remain insufficiently investigated. This study aimed to examine alterations in cholesterol synthesis and absorption by measuring plasma levels of endogenous cholesterol precursors (as markers of synthesis) and phytosterols (as indicators of absorption). A total of 124 MASLD patients and 43 healthy individuals were included. Our results showed higher plasma concentrations of lathosterol in the MASLD group (p = 0.006), in parallel with comparable concentrations of desmosterol (p = 0.472) and all analyzed phytosterols in both groups. Correlation analysis showed that both lathosterol and desmosterol were positively associated with non-invasive hepatic steatosis indices: FLI, HSI, and TyG index (p < 0.01, p < 0.01, and p < 0.05, respectively). Multivariate linear regression further confirmed that these synthesis markers remained significant predictors of FLI (p = 0.010), HSI (p = 0.013), and TyG index (p = 0.002), even after adjusting for other relevant variables. These findings indicate that MASLD is associated with a shift in cholesterol homeostasis towards enhanced endogenous cholesterol synthesis.