{"title":"Maternal betaine supplementation ameliorates fatty liver disease in offspring mice by inhibiting hepatic NLRP3 inflammasome activation.","authors":"Lun Li, Liuqiao Sun, Xiaoping Liang, Qian Ou, Xuying Tan, Fangyuan Li, Zhiwei Lai, Chenghe Ding, Hangjun Chen, Xinxue Yu, Qiongmei Wu, Jun Wei, Feng Wu, Lijun Wang","doi":"10.4162/nrp.2023.17.6.1084","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/objectives: </strong>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.</p><p><strong>Materials/methods: </strong>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.</p><p><strong>Results: </strong>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 <i>IL-6</i>, <i>IL-18</i>, and <i>Casp</i>ase-<i>1</i> were significantly higher in the FLD group than in the CD group. Maternal betaine supplementation reduced the expression of <i>IL-1β</i>, <i>IL-6</i>, <i>IL-18,</i> and apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (<i>ASC</i>). 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 <i>TNF-α</i>, <i>NLRP3</i>, <i>ASC</i>, and <i>IL-18</i>. The hepatic SAH concentration was inversely associated with the <i>IL-1β</i> mRNA expression.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":19232,"journal":{"name":"Nutrition Research and Practice","volume":"17 6","pages":"1084-1098"},"PeriodicalIF":2.0000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694418/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nutrition Research and Practice","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4162/nrp.2023.17.6.1084","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/9/19 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
Nutrition Research and Practice (NRP) is an official journal, jointly published by the Korean Nutrition Society and the Korean Society of Community Nutrition since 2007. The journal had been published quarterly at the initial stage and has been published bimonthly since 2010.
NRP aims to stimulate research and practice across diverse areas of human nutrition. The Journal publishes peer-reviewed original manuscripts on nutrition biochemistry and metabolism, community nutrition, nutrition and disease management, nutritional epidemiology, nutrition education, foodservice management in the following categories: Original Research Articles, Notes, Communications, and Reviews. Reviews will be received by the invitation of the editors only. Statements made and opinions expressed in the manuscripts published in this Journal represent the views of authors and do not necessarily reflect the opinion of the Societies.