Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice

Karen R. Jonscher, Michael S. Stewart, Alba Alfonso-Garcia, Brian C. DeFelice, Xiaoxin X. Wang, Yuhuan Luo, Moshe Levi, Margaret J.R. Heerwagen, Rachel C. Janssen, Becky A. De La Houssaye, Ellen Wiitala, Garrett Florey, Raleigh L. Jonscher, Eric O. Potma, Oliver Fiehn, Jacob E. Friedman

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Nonalcoholic fatty liver disease (NAFLD) is widespread in adults and children. Early exposure to maternal obesity orWestern-style diet (WD) increases steatosis and oxidative stress in fetal liver and is associatedwith lifetime disease risk in the offspring. Pyrroloquinoline quinone (PQQ) is a natural antioxidant found in soil, enriched in human breast milk, and essential for development in mammals. We investigated whether a supplemental dose of PQQ, provided prenatally in amousemodel of diet-induced obesity during pregnancy, could protect obese offspring from progression ofNAFLD.PQQtreatment givenpre- and postnatally inWD-fedoffspring had no effect on weight gain but increased metabolic flexibility while reducing body fat and liver lipids, compared with untreated obese offspring. Indices ofNAFLD, including hepatic ceramide levels, oxidative stress, and expression of proinflammatory genes (Nos2, Nlrp3, Il6, and Ptgs2), were decreased in WD PQQ-fed mice, concomitant with increasedexpression of fatty acid oxidation genes and decreasedPparg expression.Notably, these changespersisted even after PQQ withdrawal at weaning. Our results suggest that supplementation with PQQ, particularly during pregnancy and lactation, protects offspring fromWD-induced developmental programming of hepatic lipotoxicity and may help slow the advancing epidemic of NAFLD in the next generation.

Original languageEnglish (US)
Pages (from-to)1434-1448
Number of pages15
JournalFASEB Journal
Volume31
Issue number4
DOIs
StatePublished - Apr 1 2017

Keywords

  • Antioxidant
  • CARS
  • Ceramide
  • Lipidomics
  • PGC-1α

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice'. Together they form a unique fingerprint.

  • Cite this

    Jonscher, K. R., Stewart, M. S., Alfonso-Garcia, A., DeFelice, B. C., Wang, X. X., Luo, Y., Levi, M., Heerwagen, M. J. R., Janssen, R. C., De La Houssaye, B. A., Wiitala, E., Florey, G., Jonscher, R. L., Potma, E. O., Fiehn, O., & Friedman, J. E. (2017). Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice. FASEB Journal, 31(4), 1434-1448. https://doi.org/10.1096/fj.201600906R