The Role of p53 in Adipocyte Differentiation and Lipid Metabolism in Obese Mice via Transcriptional Regulation of Lgals3

IF 4.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Obesity Pub Date : 2025-09-02 DOI:10.1002/oby.24363
Huarui Li, Zhengze Yv, Shihua Tan, Peihua Li, Ning Jiang, Fenglin Peng
{"title":"The Role of p53 in Adipocyte Differentiation and Lipid Metabolism in Obese Mice via Transcriptional Regulation of Lgals3","authors":"Huarui Li,&nbsp;Zhengze Yv,&nbsp;Shihua Tan,&nbsp;Peihua Li,&nbsp;Ning Jiang,&nbsp;Fenglin Peng","doi":"10.1002/oby.24363","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>This study investigates the regulatory role of p53 on Lgals3 expression and its impact on preadipocyte differentiation, fatty acid synthesis, and oxidation in obesity.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Bioinformatics analysis of six obesity-related microarray datasets and single-cell RNA sequencing (scRNA-seq) data identified Lgals3 as a key obesity-associated gene. A high-fat diet (HF) mouse model was established to evaluate obesity-related phenotypes, including body weight, hepatic Lgals3 expression, adipose tissue pathology, blood lipid profiles, and glucose tolerance. In vitro experiments using 3T3-L1 cells were conducted to assess adipocyte differentiation, fatty acid synthase (FAS) activity, and glucose uptake. The interaction between p53 and the Lgals3 promoter was analyzed via dual-luciferase reporter and chromatin immunoprecipitation assays. Key metabolic genes and proteins were quantified by RT-qPCR and Western blot.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>HF mice exhibited significant weight gain, elevated Lgals3 expression, and altered lipid profiles. In vitro, p53 was shown to transcriptionally repress Lgals3, thereby reducing adipocyte differentiation, FAS activity, and glucose uptake. In vivo, p53 overexpression led to downregulation of Lgals3 and improvement in obesity-related metabolic outcomes, whereas Lgals3 overexpression counteracted these effects.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>p53 inhibits Lgals3 expression, suppressing adipocyte differentiation and improving obesity-related metabolic dysfunction, highlighting its potential as a therapeutic target in obesity management.</p>\n \n <div>\n \n <figure>\n <div><picture>\n <source></source></picture><p></p>\n </div>\n </figure>\n </div>\n </section>\n </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 10","pages":"1895-1908"},"PeriodicalIF":4.7000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24363","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Obesity","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/oby.24363","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

Abstract

Objective

This study investigates the regulatory role of p53 on Lgals3 expression and its impact on preadipocyte differentiation, fatty acid synthesis, and oxidation in obesity.

Methods

Bioinformatics analysis of six obesity-related microarray datasets and single-cell RNA sequencing (scRNA-seq) data identified Lgals3 as a key obesity-associated gene. A high-fat diet (HF) mouse model was established to evaluate obesity-related phenotypes, including body weight, hepatic Lgals3 expression, adipose tissue pathology, blood lipid profiles, and glucose tolerance. In vitro experiments using 3T3-L1 cells were conducted to assess adipocyte differentiation, fatty acid synthase (FAS) activity, and glucose uptake. The interaction between p53 and the Lgals3 promoter was analyzed via dual-luciferase reporter and chromatin immunoprecipitation assays. Key metabolic genes and proteins were quantified by RT-qPCR and Western blot.

Results

HF mice exhibited significant weight gain, elevated Lgals3 expression, and altered lipid profiles. In vitro, p53 was shown to transcriptionally repress Lgals3, thereby reducing adipocyte differentiation, FAS activity, and glucose uptake. In vivo, p53 overexpression led to downregulation of Lgals3 and improvement in obesity-related metabolic outcomes, whereas Lgals3 overexpression counteracted these effects.

Conclusions

p53 inhibits Lgals3 expression, suppressing adipocyte differentiation and improving obesity-related metabolic dysfunction, highlighting its potential as a therapeutic target in obesity management.

Abstract Image

p53通过转录调控Lgals3在肥胖小鼠脂肪细胞分化和脂质代谢中的作用
目的:探讨肥胖患者p53对Lgals3表达的调控作用及其对前脂肪细胞分化、脂肪酸合成和氧化的影响。方法:对6个肥胖相关微阵列数据集和单细胞RNA测序(scRNA-seq)数据进行生物信息学分析,确定Lgals3是一个关键的肥胖相关基因。建立了高脂饮食小鼠模型,以评估肥胖相关表型,包括体重、肝脏Lgals3表达、脂肪组织病理、血脂谱和葡萄糖耐量。利用3T3-L1细胞进行体外实验,以评估脂肪细胞分化、脂肪酸合成酶(FAS)活性和葡萄糖摄取。通过双荧光素酶报告基因和染色质免疫沉淀法分析p53和Lgals3启动子之间的相互作用。采用RT-qPCR和Western blot对关键代谢基因和蛋白进行定量分析。结果:HF小鼠表现出明显的体重增加、Lgals3表达升高和脂质谱改变。在体外实验中,p53被证明可以转录抑制Lgals3,从而降低脂肪细胞分化、FAS活性和葡萄糖摄取。在体内,p53过表达导致Lgals3的下调和肥胖相关代谢结果的改善,而Lgals3过表达抵消了这些影响。结论:p53可抑制Lgals3的表达,抑制脂肪细胞分化,改善肥胖相关代谢功能障碍,显示其作为肥胖治疗靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Obesity
Obesity 医学-内分泌学与代谢
CiteScore
11.70
自引率
1.40%
发文量
261
审稿时长
2-4 weeks
期刊介绍: Obesity is the official journal of The Obesity Society and is the premier source of information for increasing knowledge, fostering translational research from basic to population science, and promoting better treatment for people with obesity. Obesity publishes important peer-reviewed research and cutting-edge reviews, commentaries, and public health and medical developments.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信