Maternal One-Carbon Supplement Reduced the Risk of Non-Alcoholic Fatty Liver Disease in Male Offspring

Recent studies have suggested that prevention of obesity and non-alcoholic fatty liver disease (NAFLD) should start with maternal dietary management. We previously reported disrupted methionine cycle, associated with NAFLD, in male offspring liver due to maternal high-fat (HF) diet, thus we hypothes...

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Main Authors: Hui Peng, Huiting Xu, Jie Wu, Jiangyuan Li, Xian Wang, Zhimin Liu, Minjee Kim, Minsun S. Jeon, Ke K. Zhang, Linglin Xie
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/14/12/2545
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author Hui Peng
Huiting Xu
Jie Wu
Jiangyuan Li
Xian Wang
Zhimin Liu
Minjee Kim
Minsun S. Jeon
Ke K. Zhang
Linglin Xie
author_facet Hui Peng
Huiting Xu
Jie Wu
Jiangyuan Li
Xian Wang
Zhimin Liu
Minjee Kim
Minsun S. Jeon
Ke K. Zhang
Linglin Xie
author_sort Hui Peng
collection DOAJ
description Recent studies have suggested that prevention of obesity and non-alcoholic fatty liver disease (NAFLD) should start with maternal dietary management. We previously reported disrupted methionine cycle, associated with NAFLD, in male offspring liver due to maternal high-fat (HF) diet, thus we hypothesize that maternal one-carbon supplement may reduce the risk of NAFLD in offspring via the normalizing methionine cycle. To test it, female mice (F0) were exposed to either a maternal normal-fat diet (NF group) a maternal HF diet (HF group), or a maternal methyl donor supplement (H1S or H2S group) during gestation and lactation. The offspring male mice (F1) were exposed to a postweaning HF diet to promote NAFLD. While the HF offspring displayed obesity, glucose intolerance and hepatic steatosis, the H1S and H2S offspring avoided hepatic steatosis. This phenotype was associated with the normalization of the methionine cycle and the restoration of L-carnitine and AMPK activity. Furthermore, maternal HF diet induced epigenetic regulation of important genes involved in fatty acid oxidation and oxidative phosphorylation via DNA methylation modifications, which were recovered by maternal one-carbon supplementation. Our study provides evidence that maternal one-carbon supplement can reverse/block the adverse effects of maternal HF diet on promoting offspring NAFLD, suggesting a potential nutritional strategy that is administered to mothers to prevent NAFLD in the offspring.
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spelling doaj.art-9bd9682239d64f538477656d88f31bc72023-11-23T18:23:02ZengMDPI AGNutrients2072-66432022-06-011412254510.3390/nu14122545Maternal One-Carbon Supplement Reduced the Risk of Non-Alcoholic Fatty Liver Disease in Male OffspringHui Peng0Huiting Xu1Jie Wu2Jiangyuan Li3Xian Wang4Zhimin Liu5Minjee Kim6Minsun S. Jeon7Ke K. Zhang8Linglin Xie9Department of Nutrition, Texas A&M University, College Station, TX 77840, USADepartment of Pathology, University of North Dakota, Grand Forks, ND 58202, USACenter for Epigenetics & Disease Prevention, Institute of Biosciences & Technology, College of Medicine, Texas A&M University, Houston, TX 77840, USADepartment of Statistics, Texas A&M University, College Station, TX 77840, USADepartment of Nutrition, Texas A&M University, College Station, TX 77840, USADepartment of Nutrition, Texas A&M University, College Station, TX 77840, USADepartment of Statistics, Texas A&M University, College Station, TX 77840, USACenter for Epigenetics & Disease Prevention, Institute of Biosciences & Technology, College of Medicine, Texas A&M University, Houston, TX 77840, USADepartment of Nutrition, Texas A&M University, College Station, TX 77840, USADepartment of Nutrition, Texas A&M University, College Station, TX 77840, USARecent studies have suggested that prevention of obesity and non-alcoholic fatty liver disease (NAFLD) should start with maternal dietary management. We previously reported disrupted methionine cycle, associated with NAFLD, in male offspring liver due to maternal high-fat (HF) diet, thus we hypothesize that maternal one-carbon supplement may reduce the risk of NAFLD in offspring via the normalizing methionine cycle. To test it, female mice (F0) were exposed to either a maternal normal-fat diet (NF group) a maternal HF diet (HF group), or a maternal methyl donor supplement (H1S or H2S group) during gestation and lactation. The offspring male mice (F1) were exposed to a postweaning HF diet to promote NAFLD. While the HF offspring displayed obesity, glucose intolerance and hepatic steatosis, the H1S and H2S offspring avoided hepatic steatosis. This phenotype was associated with the normalization of the methionine cycle and the restoration of L-carnitine and AMPK activity. Furthermore, maternal HF diet induced epigenetic regulation of important genes involved in fatty acid oxidation and oxidative phosphorylation via DNA methylation modifications, which were recovered by maternal one-carbon supplementation. Our study provides evidence that maternal one-carbon supplement can reverse/block the adverse effects of maternal HF diet on promoting offspring NAFLD, suggesting a potential nutritional strategy that is administered to mothers to prevent NAFLD in the offspring.https://www.mdpi.com/2072-6643/14/12/2545non-alcoholic fatty liver disease (NAFLD)pregnancyoffspringhigh-fat dietone-carbon supplementepigenetics
spellingShingle Hui Peng
Huiting Xu
Jie Wu
Jiangyuan Li
Xian Wang
Zhimin Liu
Minjee Kim
Minsun S. Jeon
Ke K. Zhang
Linglin Xie
Maternal One-Carbon Supplement Reduced the Risk of Non-Alcoholic Fatty Liver Disease in Male Offspring
Nutrients
non-alcoholic fatty liver disease (NAFLD)
pregnancy
offspring
high-fat diet
one-carbon supplement
epigenetics
title Maternal One-Carbon Supplement Reduced the Risk of Non-Alcoholic Fatty Liver Disease in Male Offspring
title_full Maternal One-Carbon Supplement Reduced the Risk of Non-Alcoholic Fatty Liver Disease in Male Offspring
title_fullStr Maternal One-Carbon Supplement Reduced the Risk of Non-Alcoholic Fatty Liver Disease in Male Offspring
title_full_unstemmed Maternal One-Carbon Supplement Reduced the Risk of Non-Alcoholic Fatty Liver Disease in Male Offspring
title_short Maternal One-Carbon Supplement Reduced the Risk of Non-Alcoholic Fatty Liver Disease in Male Offspring
title_sort maternal one carbon supplement reduced the risk of non alcoholic fatty liver disease in male offspring
topic non-alcoholic fatty liver disease (NAFLD)
pregnancy
offspring
high-fat diet
one-carbon supplement
epigenetics
url https://www.mdpi.com/2072-6643/14/12/2545
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