The role of KLF2 in regulating hepatic lipogenesis and blood cholesterol homeostasis via the SCAP/SREBP pathway
作者全名："Huang, Yuhong; Wang, Yi Fan; Ruan, Xiong Zhong; Lau, Chi Wai; Wang, Li; Huang, Yu"
作者地址："[Huang, Yuhong; Wang, Li; Huang, Yu] City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Peoples R China; [Huang, Yuhong; Wang, Yi Fan; Lau, Chi Wai] Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Peoples R China; [Huang, Yuhong] Chinese Univ Hong Kong, Shenzhen Res Inst, Shenzhen, Peoples R China; [Huang, Yuhong] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Shenzhen, Peoples R China; [Ruan, Xiong Zhong] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Ctr Lipid Res,Dept Infect Dis, Chongqing, Peoples R China; [Ruan, Xiong Zhong] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infect Dis,Key Lab Mol Biol Infect Dis,Minist, Chongqing, Peoples R China"
通信作者："Huang, Y (通讯作者)，City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Peoples R China."
来源：JOURNAL OF LIPID RESEARCH
ESI学科分类：BIOLOGY & BIOCHEMISTRY
WOS号：WOS:001166096100001
JCR分区：Q1
影响因子：6.5
年份：2024
卷号：65
期号：1
开始页：
结束页：
文献类型：Article
关键词：
摘要："Liver steatosis is a common metabolic dis-order resulting from imbalanced lipid metabolism, which involves various processes such as de novo lipogenesis, fatty acid uptake, fatty acid oxidation, and VLDL secretion. In this study, we discovered that KLF2, a transcription factor, plays a crucial role in regulating lipid metabolism in the liver. Over-expression of KLF2 in the liver of db/db mice, C57BL/6J mice, and Cd36-/- mice fed on a normal diet resulted in increased lipid content in the liver. Additionally, transgenic mice (ALB-Klf2) that overexpressed Klf2 in the liver developed liver steatosis after being fed a normal diet. We found that KLF2 promotes lipogen-esis by increasing the expression of SCAP, a chaperone that facilitates the activation of SREBP, the master transcription factor for lipogenic gene expression. Our mechanism studies revealed that KLF2 enhances lipogenesis in the liver by binding to the promoter of SCAP and increasing the expression of genes involved in fatty acid synthesis. Reduction of KLF2 expression led to a decrease in SCAP expression and a reduction in the expression of SREBP1 target genes involved in lipogenesis. Overexpression of KLF2 also increased the activation of SREBP2 and the mRNA levels of its downstream target SOAT1. In C57BL/6Jmice fed a high-fat diet, overexpression of Klf2 increased blood VLDL secretion, while reducing its expression decreased blood cholesterol levels. Our study emphasizes the novelty that hepatic KLF2 plays a critical role in regulating lipid metabolism through the KLF2/SCAP/ SREBPs pathway, which is essential for hepatic lipo-genesis and maintaining blood cholesterol homeostasis."
基金机构："National Natural Science Foundation of China [82003820, 91939302]; Research Grants Council of Hong Kong [SRFS2021-4S04, 14109720, AoEM-707/18, R4012-18]"
基金资助正文："This study is supported by National Natural Science Foundation of China (82003820, 91939302) and the Research Grants Council of Hong Kong (SRFS2021-4S04, 14109720, AoEM-707/18, R4012-18) ."
