Journal Article

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

Aagaard, Kjersti M., McCurdy, Carrie E., Nash, Michael J., Gannon, Maureen, Friedman, Jacob E., Newsom, Sean A., Messaoudi, Ilhem, Janssen, Rachel C., Dobrinskikh, Evgenia, Wesolowski, Stephanie R., Kievit, Paul

2021

Overview

Maternal obesity affects nearly one-third of pregnancies and is a major risk factor for nonalcoholic fatty liver disease (NAFLD) in adolescent offspring, yet the mechanisms behind NAFLD remain poorly understood. Here, we demonstrate that nonhuman primate fetuses exposed to maternal Western-style diet (WSD) displayed increased fibrillar collagen deposition in the liver periportal region, with increased ACTA2 and TIMP1 staining, indicating localized hepatic stellate cell (HSC) and myofibroblast activation. This collagen deposition pattern persisted in 1-year-old offspring, despite weaning to a control diet (CD). Maternal WSD exposure increased the frequency of DCs and reduced memory CD4+ T cells in fetal liver without affecting systemic or hepatic inflammatory cytokines. Switching obese dams from WSD to CD before conception or supplementation of the WSD with resveratrol decreased fetal hepatic collagen deposition and reduced markers of portal triad fibrosis, oxidative stress, and fetal hypoxemia. These results demonstrate that HSCs and myofibroblasts are sensitive to maternal WSD-associated oxidative stress in the fetal liver, which is accompanied by increased periportal collagen deposition, indicative of early fibrogenesis beginning in utero. Alleviating maternal WSD-driven oxidative stress in the fetal liver holds promise for halting steatosis and fibrosis and preventing developmental programming of NAFLD.

• Publisher: American Society for Clinical Investigation,American Society for Clinical investigation
• Subject: Animals / Birth weight / CD4 antigen / Cell activation / Childhood / Collagen / Diet / Diet, Western - adverse effects / Fatty liver / Female / Females / Fetuses / Fibrosis / Gastroenterology / Hepatocytes / Hypoxemia / Immunological memory / Inflammation / Insulin resistance / Liver Cirrhosis - physiopathology / Liver diseases / Lymphocytes T / Maternal Exposure / Maternal Nutritional Physiological Phenomena - physiology / Memory cells / Metabolic disorders / Obesity / Offspring / Oxidative stress / Pediatrics / Pregnancy / Primates / Resveratrol / Risk factors / Steatosis / Tissue inhibitor of metalloproteinase 1 / Uterus / Veins & arteries / Weaning