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Forkhead Box A3 and Bile Acid Metabolism

叉头盒 A3 和胆汁酸代谢

基本信息

批准号：
10546499
负责人：
Yanqiao Zhang
金额：
$ 53.56万
依托单位：
NORTHEAST OHIO MEDICAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10546499
关键词：
Agonist Anabolism Bile Acid Biosynthesis Pathway Bile Acids CYP7A1 gene CYP8B1 gene Cholestasis Cholesterol Circulation Coupled Data Diabetes Mellitus Diet Dietary Fats Disease Endocrine Energy Metabolism Enzymes FGF19 gene Fat-Soluble Vitamin Fatty Liver Fatty acid glycerol esters Feedback Fibroblast Growth Factor G-Protein-Coupled Receptors GPBAR1 gene GTP-Binding Proteins Generations Goals Health Hepatic Hepatocyte High Fat Diet Homeostasis Hormones Human Hydroxylation Impairment Incidence Inflammation Insulin Resistance Intestines Lipids Liver MAPK8 gene Malabsorption Syndromes Mediating Metabolic Metabolic Diseases Metabolic stress Mitogen-Activated Protein Kinase Kinases Mitogen-Activated Protein Kinases Mixed Function Oxygenases Mus Nuclear Hormone Receptors Obese Mice Obesity Patients Play Production Proteins Receptor Activation Receptor Inhibition Regulation Role Signal Transduction Sterols Testing Transgenic Organisms Vitamin D3 Receptor Work absorption bile acid metabolism blood glucose regulation chronic liver disease diabetic diet-induced obesity farnesoid X-activated receptor gain of function gallstone disease glucose metabolism hypercholesterolemia improved knock-down lipid metabolism liver growth factor liver metabolism loss of function member non-alcoholic fatty liver disease nonalcoholic steatohepatitis novel novel therapeutic intervention nutrient absorption overexpression pregnane X receptor prevent receptor transcription factor uptake

项目摘要

Project Summary Project Summary: Bile acids (BAs) are synthesized from cholesterol. BA synthesis is tightly controlled to prevent incidence of diseases, such as cholestasis, gallstone disease, malabsorption, hypercholesterolemia, etc. BAs are important for nutrient absorption and also function as endocrine hormones to regulate metabolic homeostasis. BAs can activate farnesoid X receptor (FXR) and TGR5 to prevent non-alcoholic fatty liver disease (NAFLD), diabetes and obesity. NAFLD is one of the most common chronic liver diseases worldwide, and is often associated with obesity and diabetes. Forkhead box protein A3 (FOXA3) is a transcription factor. So far, the role of hepatic FOXA3 in BA metabolism is completely unknown. Using both gain- and loss-of-function approaches, we show that FOXA3 is regulated by FXR and may regulate BA metabolism and metabolic homeostasis. In this project, we plan to investigate the role of hepatic FOXA3 in feedback regulation of BA metabolism and the role of BA signaling in FOXA3-regulated metabolic homeostasis. We will use a number of genetically modified mice as well as gain-of-function approaches to accomplish our goals.

项目摘要胆汁酸（Bile Acids，BAs）是由胆固醇合成的。BA合成受到严格控制，预防胆汁淤积、胆结石、吸收不良、高胆固醇血症等疾病的发生。 BA对营养吸收很重要，也作为内分泌激素调节代谢体内平衡BA可以激活法尼醇X受体（FXR）和TGR 5，以预防非酒精性脂肪肝疾病（NAFLD）、糖尿病和肥胖。NAFLD是全球最常见的慢性肝病之一，通常与肥胖和糖尿病有关。叉头盒蛋白A3（FOXA 3）是一种转录因子。到目前为止，肝FOXA 3在BA代谢中的作用完全未知。同时使用功能增益和功能损失方法，我们表明FOXA 3受FXR调节，并可能调节BA代谢和代谢体内平衡。在本项目中，我们计划研究肝脏FOXA 3在BA反馈调节中的作用，代谢和BA信号转导在FOXA 3调节的代谢稳态中的作用。我们将使用一些转基因小鼠以及获得功能的方法来实现我们的目标。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Hepatocyte nuclear factor 4α in the pathogenesis of non-alcoholic fatty liver disease.

DOI：
10.1097/cm9.0000000000002092
发表时间：
2022-05-20
期刊：
Chinese medical journal
影响因子：
6.1
作者：
通讯作者：

Deletion of hepatic small heterodimer partner ameliorates development of nonalcoholic steatohepatitis in mice.

DOI：
10.1016/j.jlr.2023.100454
发表时间：
2023-11
期刊：
JOURNAL OF LIPID RESEARCH
影响因子：
6.5
作者：
Lee, Yoon-Kwang;Park, Jung Eun;Lee, Mikang;Mifflin, Ryan;Xu, Yang;Novak, Robert;Zhang, Yanqiao;Hardwick, James P.
通讯作者：
Hardwick, James P.

Hepatocyte Sirtuin 6 Protects against Atherosclerosis and Steatohepatitis by Regulating Lipid Homeostasis.

DOI：
10.3390/cells12152009
发表时间：
2023-08-05
期刊：
CELLS
影响因子：
6
作者：
Zhu, Yingdong;Hu, Shuwei;Pan, Xiaoli;Gopoju, Raja;Bawa, Fathima Cassim N.;Yin, Liya;Xu, Yanyong;Zhang, Yanqiao
通讯作者：
Zhang, Yanqiao

Hepatocyte Nuclear Factor 4α Prevents the Steatosis-to-NASH Progression by Regulating p53 and Bile Acid Signaling (in mice).

DOI：
10.1002/hep.31604
发表时间：
2021-06
期刊：
Hepatology (Baltimore, Md.)
影响因子：
0
作者：
Xu Y;Zhu Y;Hu S;Xu Y;Stroup D;Pan X;Bawa FC;Chen S;Gopoju R;Yin L;Zhang Y
通讯作者：
Zhang Y

Hepatocytic Activating Transcription Factor 3 Protects Against Steatohepatitis via Hepatocyte Nuclear Factor 4α.

肝细胞激活转录因子 3 通过肝细胞核因子 4α 预防脂肪性肝炎。

DOI：
10.2337/db21-0181
发表时间：
2021
期刊：
Diabetes
影响因子：
7.7
作者：
Xu,Yanyong;Hu,Shuwei;Jadhav,Kavita;Zhu,Yingdong;Pan,Xiaoli;Bawa,FathimaCassim;Yin,Liya;Zhang,Yanqiao
通讯作者：
Zhang,Yanqiao