Maternal Western diet exposure increases periportal fibrosis beginning in utero in nonhuman primate offspring

Area of Science:

• Reproductive biology
• Hepatology
• Developmental programming

Background:

• Maternal obesity is a significant risk factor for nonalcoholic fatty liver disease (NAFLD) in adolescent offspring.
• The underlying mechanisms linking maternal obesity to offspring NAFLD are not fully understood.

Purpose of the Study:

• To investigate the effects of maternal Western-style diet (WSD) on fetal liver development and early fibrogenesis in nonhuman primates.
• To explore potential interventions to mitigate WSD-induced liver changes in offspring.

Main Methods:

• Nonhuman primate model exposed to maternal WSD during gestation.
• Analysis of fetal and 1-year-old offspring liver tissue for collagen deposition, hepatic stellate cell (HSC) activation markers (ACTA2, TIMP1), and immune cell populations.
• Assessment of interventions including dietary changes (WSD to control diet) and resveratrol supplementation.

Main Results:

• Maternal WSD exposure led to increased fibrillar collagen deposition and HSC activation in fetal livers, persisting into offspring.
• WSD altered fetal liver immune cell composition (increased DCs, reduced memory CD4+ T cells).
• Dietary changes or resveratrol supplementation reduced fetal hepatic collagen deposition, fibrosis markers, oxidative stress, and hypoxemia.

Conclusions:

• Maternal WSD induces early fibrogenesis in the fetal liver via HSC activation, linked to oxidative stress.
• Periportal collagen deposition and HSC activation in utero indicate developmental programming of NAFLD.
• Alleviating maternal oxidative stress is a promising strategy to prevent NAFLD development in offspring.