Maternal Dyslipidaemia Aggravates Offspring Metabolic Dysfunction-Associated Steatotic Liver Disease

Area of Science:

• Metabolic Liver Disease
• Developmental Programming
• Nutritional Science

Background:

• Paediatric metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) have severe histopathology.
• Maternal metabolic health may predetermine offspring susceptibility to MASLD.

Purpose of the Study:

• To investigate the impact of maternal dyslipidaemia and low vitamin C (VitC) on offspring MASLD development.
• To utilize a validated guinea pig model for studying maternal-offspring metabolic programming.

Main Methods:

• Female guinea pigs were fed low-fat (LF) or high-fat (HF) diets, with or without reduced VitC, during pregnancy.
• Offspring were assessed at birth and after 10 weeks on postweaning LF or HF diets.
• Evaluated parameters included hepatic lipids, liver enzymes (ALT), liver-to-body weight ratio, fibrosis, and MASLD activity scores.

Main Results:

• Maternal HF diet induced dyslipidaemia and elevated liver enzymes in dams, without obesity.
• Offspring exposed to maternal HF diet showed increased neonatal hepatic lipids and ALT.
• Postnatal HF diet exacerbated liver fibrosis and MASLD scores in offspring; maternal HF diet with low VitC significantly reduced offspring viability.

Conclusions:

• Maternal HF diet exposure, even if brief and independent of obesity, adversely impacts offspring MASLD risk.
• Low maternal VitC status in conjunction with HF diet severely compromises offspring survival.
• Early nutritional interventions are crucial for preventing paediatric MASLD and improving offspring outcomes.