叉头盒 A3 和胆汁酸代谢-猫眼课题宝

叉头盒 A3 和胆汁酸代谢

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

项目状态：

未结题

起止时间：

2020-02-01 至 2025-01-31

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

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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.

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