Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
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Maternal betaine supplementation ameliorates fatty liver disease in offspring mice by inhibiting hepatic NLRP3 inflammasome activation

  • Lun Li (Department of Delivery Room, Guangzhou Women and Children's Medical Center) ;
  • Liuqiao Sun (Department of Maternal, Child and Adolescent Health, School of Medicine, Jinan University) ;
  • Xiaoping Liang (Department of Nutrition, School of Medicine, Jinan University) ;
  • Qian Ou (Department of Nutrition, School of Medicine, Jinan University) ;
  • Xuying Tan (Department of Child Health Care, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health) ;
  • Fangyuan Li (Department of Nutrition, School of Medicine, Jinan University) ;
  • Zhiwei Lai (Department of Nutrition, School of Medicine, Jinan University) ;
  • Chenghe Ding (Department of Nutrition, School of Medicine, Jinan University) ;
  • Hangjun Chen (Department of Nutrition, School of Medicine, Jinan University) ;
  • Xinxue Yu (Department of Nutrition, School of Medicine, Jinan University) ;
  • Qiongmei Wu (Department of Nutrition, School of Medicine, Jinan University) ;
  • Jun Wei (Department of Science and Technology, Guangzhou Customs) ;
  • Feng Wu (Department of Science and Technology, Guangzhou Customs) ;
  • Lijun Wang (Department of Nutrition, School of Medicine, Jinan University)
  • Received : 2023.04.14
  • Accepted : 2023.08.14
  • Published : 2023.12.01
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Abstract

BACKGROUND/OBJECTIVES: Previous research has shown maternal betaine supplementation alleviates fetal-derived hepatic steatosis. Therefore, this study examined the anti-inflammatory effect of maternal betaine intake in offspring mice and its mechanism. MATERIALS/METHODS: Female C57BL/6J mice and their offspring were randomly divided into 3 groups according to the treatment received during gestation and lactation: control diet (CD), fatty liver disease (FLD), and fatty liver disease + 1% betaine (FLD-BET). The FLD group was given a high-fat diet and streptozotocin (HFD + STZ), and the FLD-BET group was treated with HFD + STZ + 1% betaine. After weaning, the offspring mice were given a normal diet for 5 weeks and then dissected to measure the relevant indexes. RESULTS: Compared to the CD group, the offspring mice in the FLD group revealed obvious hepatic steatosis and increased serum levels of alanine aminotransferase, interleukin (IL)-6, and tumor necrosis factor (TNF)-α; maternal betaine supplementation reversed these changes. The hepatic mRNA expression levels of IL-6, IL-18, and Caspase-1 were significantly higher in the FLD group than in the CD group. Maternal betaine supplementation reduced the expression of IL-1β, IL-6, IL-18, and apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC). Maternal betaine supplementation also reversed the increasing protein expressions of nitric oxide dioxygenase-like receptor family pyrin domain containing 3 (NLRP3), ASC, Caspase-1, IL-1β, and IL-18 in offspring mice exposed to HFD + STZ. Maternal betaine supplementation decreased the homocysteine (Hcy) and s-adenosine homocysteine (SAH) levels significantly in the livers. Furthermore, the hepatic Hcy concentrations showed significant inverse relationships with the mRNA expression of TNF-α, NLRP3, ASC, and IL-18. The hepatic SAH concentration was inversely associated with the IL-1β mRNA expression. CONCLUSIONS: The lipotropic and anti-inflammatory effect of maternal betaine supplementation may be associated with the inhibition of NLRP3 inflammasome in the livers of the offspring mice.

Keywords

Acknowledgement

This research was funded by the Guangdong Basic and Applied Basic Research Foundation (Grant number: 2023A1515030168) and the Scientific Research Fund of China Nutrition Society (Grant numbers: CNS-HPNK2021-44). The funder did not participate in our article.

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