Location: Children's Nutrition Research Center
Project Number: 3092-10700-069-001-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Apr 1, 2024
End Date: Mar 31, 2029
Objective:
Objective 1: Define the role of hepatocyte reduced folate transporter, SLC19A1, in the progression of non-alcoholic fatty liver diseases (NAFLD).
Objective 2: Determine the role of phenylalanine metabolism of both the host and microbiome in non-alcoholic fatty liver diseases (NAFLD) development.
Approach:
With the prevalence of obesity and diabetes, non-alcoholic fatty liver diseases (NAFLD) are a major health challenge globally. Yet, the etiology of NAFLD remains unclear. We will investigate the roles of folate and amino acid metabolism in the development and progression of western diet induced NAFLD. SLC19A1 is a ubiquitously expressed folate transporter; however, the roles of folate and its major transporter SLC19A1 in the development of NAFLD are not well-defined. Thus, in Obj. 1 we will test our hypothesis that SLC19A1 in hepatocytes and folate deficiency will exacerbate NAFLD in the context of diet-induced obesity. Epidemiological studies have shown correlations of aberrant amino acid profile with different stages of NAFLD. Yet, the role of amino acid metabolism in the onset and progression of fatty liver diseases remains largely unknown. Phenylalanine is an essential amino acid that has been found at high concentrations in the circulation of patients with steatohepatitis (NASH) and fibrosis. Thus, in Obj. 2 we will test our hypothesis that nutritional availability of phenylalanine alters the gut microbiota to affect host metabolism and susceptibility to NAFLD. Together, the results will reveal the importance of folate and phenylalanine metabolism in NAFLD.
