TitleMaternal Western diet exposure increases periportal fibrosis beginning in utero in nonhuman primate offspring.
Publication TypeJournal Article
Year of Publication2021
AuthorsNash, MJ, Dobrinskikh, E, Newsom, SA, Messaoudi, I, Janssen, RC, Aagaard, KM, McCurdy, CE, Gannon, M, Kievit, P, Friedman, JE, Wesolowski, SR
JournalJCI Insight
Date Published12/2021

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.

Alternate JournalJCI Insight
PubMed ID34935645
Grant ListP51 OD011092 / OD / NIH HHS / United States
R24 DK090964 / DK / NIDDK NIH HHS / United States
F30 DK122672 / DK / NIDDK NIH HHS / United States
R01 DK108910 / DK / NIDDK NIH HHS / United States
P30 DK048520 / DK / NIDDK NIH HHS / United States
P30 NS048154 / NS / NINDS NIH HHS / United States
P30 DK116073 / DK / NIDDK NIH HHS / United States