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FASEB J. 2017 Apr;31(4):1434-1448. doi: 10.1096/fj.201600906R. Epub 2016 Dec 22.

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

Author information

1
Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; karen.jonscher@ucdenver.edu.
2
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado USA.
3
Beckman Laser Institute, and.
4
West Coast Metabolomics Center, University of California, Davis, Davis, CA USA.
5
Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
6
Department of Integrative Biology, University of Colorado, Denver, Denver, Colorado, USA; and.
7
Department of Biomedical Engineering,University of California, Irvine, Irvine, California, USA.
8
Biochemistry Department, King Abdulaziz University, Jeddah, Saudi Arabia.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is widespread in adults and children. Early exposure to maternal obesity or Western-style diet (WD) increases steatosis and oxidative stress in fetal liver and is associated with 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 a mouse model of diet-induced obesity during pregnancy, could protect obese offspring from progression of NAFLD. PQQ treatment given pre- and postnatally in WD-fed offspring had no effect on weight gain but increased metabolic flexibility while reducing body fat and liver lipids, compared with untreated obese offspring. Indices of NAFLD, 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 increased expression of fatty acid oxidation genes and decreased Pparg expression. Notably, these changes persisted even after PQQ withdrawal at weaning. Our results suggest that supplementation with PQQ, particularly during pregnancy and lactation, protects offspring from WD-induced developmental programming of hepatic lipotoxicity and may help slow the advancing epidemic of NAFLD in the next generation.-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. Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice.

KEYWORDS:

CARS; PGC-1α; antioxidant; ceramide; lipidomics

PMID:
28007783
PMCID:
PMC5349805
DOI:
10.1096/fj.201600906R
[Indexed for MEDLINE]
Free PMC Article

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