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 language | English (US) |
|---|---|
| Pages (from-to) | 1434-1448 |
| Number of pages | 15 |
| Journal | FASEB Journal |
| Volume | 31 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2017 |
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Keywords
- Antioxidant
- CARS
- Ceramide
- Lipidomics
- PGC-1α
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics
Cite this
Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice. / Jonscher, Karen R.; Stewart, Michael S.; Alfonso-Garcia, Alba; DeFelice, Brian C.; Wang, Xiaoxin X.; Luo, Yuhuan; Levi, Moshe; Heerwagen, Margaret J.R.; Janssen, Rachel C.; De La Houssaye, Becky A.; Wiitala, Ellen; Florey, Garrett; Jonscher, Raleigh L.; Potma, Eric O.; Fiehn, Oliver; Friedman, Jacob E.
In: FASEB Journal, Vol. 31, No. 4, 01.04.2017, p. 1434-1448.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice
AU - Jonscher, Karen R.
AU - Stewart, Michael S.
AU - Alfonso-Garcia, Alba
AU - DeFelice, Brian C.
AU - Wang, Xiaoxin X.
AU - Luo, Yuhuan
AU - Levi, Moshe
AU - Heerwagen, Margaret J.R.
AU - Janssen, Rachel C.
AU - De La Houssaye, Becky A.
AU - Wiitala, Ellen
AU - Florey, Garrett
AU - Jonscher, Raleigh L.
AU - Potma, Eric O.
AU - Fiehn, Oliver
AU - Friedman, Jacob E.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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.
AB - 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.
KW - Antioxidant
KW - CARS
KW - Ceramide
KW - Lipidomics
KW - PGC-1α
UR - http://www.scopus.com/inward/record.url?scp=85017311162&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85017311162&partnerID=8YFLogxK
U2 - 10.1096/fj.201600906R
DO - 10.1096/fj.201600906R
M3 - Article
AN - SCOPUS:85017311162
VL - 31
SP - 1434
EP - 1448
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 4
ER -