Recipient Organization
OKLAHOMA STATE UNIVERSITY
(N/A)
STILLWATER,OK 74078
Performing Department
(N/A)
Non Technical Summary
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in the United States, affecting approximately 80 million adults. Importantly, risk factors for the development of NAFLD tend to increase in prevalence with advancing age. The pathogenesis of NAFLD has been considered as developing from prevalent multiple parallel factors, including gut-liver axis, inflammatory pathways, and the high-fat Western diets. NAFLD displays key characteristics, such as intestinal dysbiosis and gut permeability. Identification of previously unrecognized molecules contributing to NAFLD via gut-liver axis will help to understand the action mechanisms further and to develop efficient prevention strategies. Growing evidence indicates that the endocannabinoid system (ECS) is intimately involved in the development of obesity and type 2 diabetes (T2D), the earliest metabolic driver of NAFLD, mainly by activating the cannabinoid 1 receptor (CB1R) to target central and peripheral sites such as the liver. The previous studies discovered that L-theanine, a non-protein water-soluble amino acid characteristically found in tea plants, can bind to CB1R and inhibit its activity. Thus, the objective of this project is to determine the role of CB1R via gut-liver axis in the tea bioactivities. The results of this project will have significant implications by providing fundamental guidelines and justification for development of future projects examining the effects of food and gut health on NAFLD.
Animal Health Component
(N/A)
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Goals / Objectives
The long-term goal of this project is to understand how natural products, tea leaves, consumption prevents nonalcoholic fatty liver disease (NAFLD) via the gut microbiome alterations and gut health in diet-induced obese mouse model, and how tea L-theanine, as a potential bioactive compound, exerts the protective role in this disease process. Our project aims to bridge this knowledge gap, investigating how tea leaves impact gut health by modifying the gut microbiome in cannabinoid 1 receptor (CB1R)-mediated NAFLD. Specifically, we are exploring whether consuming tea leaves as a whole food can promote gut health in this context.
Project Methods
Our first working hypothesis isthat tea products protect impaired metabolic function and gut microbialhomeostasis through cannabinid 1 receptor (CB1R) agonism in diet-induced obese mice. We will investigate this by assessing the effect of green tea combined with CB1R agonism (ACEA) or antagonism (JD 5037) in diet-induced obese male and female mice, examining hepatic fat accumulation, glucose and lipid metabolism. The second working hypothesis isthat L-theanine, a tea bioactive compound, mitigates hepatic CB1R-dependent metabolic abnormalities and rebalances beneficial and pathogenic bacteria ratios. We will explore the role of L-theanine in preventing metabolic dysregulation and restoring gut microbial populations influenced by CB1R in the nutritionally challenged liver specific CB1KO mice.