Maternal Dyslipidaemia Aggravates Offspring Metabolic Dysfunction-Associated Steatotic Liver Disease.

Abstract

Paediatric metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) display a distinct and severe histopathology. Maternal metabolic status may program offspring susceptibility to MASLD. This study investigated if maternal dyslipidaemia and low vitamin C (VitC) status influence offspring MASLD using a validated guinea pig model. Thirty female guinea pigs received a low-fat (LF) diet until pregnancy was confirmed, then remained on LF or switched to a high-fat (HF) diet with or without reduced VitC. Offspring were evaluated at birth and after 10 weeks on postweaning HF or LF diets. In dams, HF diet induced dyslipidaemia and elevated hepatic triglycerides and alanine aminotransferase (ALT) compared to LF dams, without causing obesity. Newborns exposed to maternal HF diet showed increased hepatic triglycerides, liver-to-body weight ratio and ALT. By 10 weeks, liver fibrosis and MASLD activity scores were higher in offspring maintained on a postnatal HF diet compared to LF. Notably, offspring viability was markedly reduced on maternal HF diet with low VitC. These findings demonstrate that even short exposure to maternal HF diet, independent of obesity, can adversely affect offspring MASLD risk and highlight the need for early prevention. Additionally, findings support the need to investigate interactions between maternal diet, VitC status and offspring survival.