Proteomic Analysis of One-carbon Metabolism-related Marker in Liver of Rat Offspring.
Maternal food intake has a significant effect on the fetal environment, and an inadequate maternal diet may result in intrauterine growth restriction. Intrauterine growth restriction newborn rat pups nursed by normal diet-fed dams exhibited rapid catch-up growth, which plays a critical role in the risk for metabolic and cardiovascular disease in later life. Specifically, one-carbon metabolism in the liver plays a critical role in placental and fetal growth. Impaired functioning of one-carbon metabolism is associated with increased homocysteine levels. In this study, we applied a comprehensive proteomic approach to identify differential expression of proteins related to one-carbon metabolism in the livers of rat offspring as an effect of maternal food restriction during gestation. Data are available via ProteomeXchange with identifier PXD002578. We determined that betaine-homocysteine S-methyltransferase 1, methylenetetrahydrofolate dehydrogenase 1, and ATP synthase subunit beta mitochondrial (ATP5B) expression levels were significantly reduced in the livers of rat offspring exposed to maternal food restriction during gestation compared with in the offspring of rats fed a normal diet (p < 0.05). Moreover, the expression levels of betaine-homocysteine S-methyltransferase 1, methylenetetrahydrofolate dehydrogenase 1, and ATP synthase subunit beta mitochondrial were negatively correlated with serum homocysteine concentration in male offspring exposed to maternal food restriction during gestation and normal diet during lactation. However, in female offspring only expression levels of methylenetetrahydrofolate dehydrogenase 1 were negatively correlated with homocysteine concentration. This study shows that maternal food restriction during late gestation and normal diet during lactation lead to increased homocysteine concentration through disturbance of one-carbon metabolism in the livers of male offspring. This suggests that male offspring have an increased gender-specific susceptibility to disease in later life through fetal programming.
From the ‡Medical Research Institute, School of Medicine, Ewha Womans University, Seoul 158-710, Korea;
Young-Ah
YA
You
§Department of Obstetrics and Gynecology, Ewha Womans University, Seoul, 158-710, Korea;
Ji Hye
JH
Lee
§Department of Obstetrics and Gynecology, Ewha Womans University, Seoul, 158-710, Korea;
Eun Jin
EJ
Kwon
From the ‡Medical Research Institute, School of Medicine, Ewha Womans University, Seoul 158-710, Korea;
Jae Young
JY
Yoo
¶Department of Animal Science and Technology, Chung-Ang University, Anseong, Gyeonggi-Do 456-756, Korea.
Woo-Sung
WS
Kwon
¶Department of Animal Science and Technology, Chung-Ang University, Anseong, Gyeonggi-Do 456-756, Korea.
Myung-Geol
MG
Pang
From the ‡Medical Research Institute, School of Medicine, Ewha Womans University, Seoul 158-710, Korea; §Department of Obstetrics and Gynecology, Ewha Womans University, Seoul, 158-710, Korea; kkyj@ewha.ac.kr.
Young Ju
http://orcid.org/0000-0002-3153-3008
YJ
Kim
D000818:Animals; D050940:Betaine-Homocysteine S-Methyltransferase / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D031204:Caloric Restriction; D002244:Carbon / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006710:Homocysteine / Q000097:blood; D007774:Lactation / Q000502:physiology; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D001786:Blood Glucose; D006710:Homocysteine; D002244:Carbon; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D050940:Betaine-Homocysteine S-Methyltransferase; C497342:ATP synthase beta subunit, rat; D025261:Mitochondrial Proton-Translocating ATPases