Regulation of NFkappaB-Mediated Inflammation By Green Tea in Obese Models of Nonalcoholic Steatohepatitis
Year: 2017
Type: article
Abstract: Green tea extract (GTE) protects against nuclear factor κB (NFκB)-mediated liver inflammation during nonalcoholic steatohepatitis (NASH).However, the mechanisms by which GTE exerts its antiinflammatory activities during NASH are unclear.There are several potential pathways and environmental conditions that mediate hepatic NFκB activation during NASH, including intracellular oxidative stress that is downregulated by nuclear factor E2-related factor 2 (Nrf2)-dependent antioxidant defenses, as well as the extracellular receptor-mediated pathways toll-like receptor 4 (TLR4) and tumor necrosis factor receptor 1 (TNFR1).Therefore, this dissertation aimed to define the involvement of these pathways in relation to antiinflammatory activities of GTE on hepatic NFκB activation during NASH.The central hypothesis was that GTE suppresses hepatic NFκB activation by increasing the activities of Nrf2, and by decreasing TLR4-and TNFR1-mediated signaling.Contrary to the hypothesis, studies in Nrf2-knockout mice demonstrated that GTE exerts its antiinflammatory activities against NFκB activation during NASH in an Nrf2-independent manner.Studies in wildtype mice that were fed with low-fat (LF) or high-fat (HF) diet containing 0 or 2% GTE demonstrated that GTE lowers NFκB-dependent inflammatory responses by reducing ligand availability for, and receptor expression of, TNFR1 and TLR4 pathways.Also, GTE protects against metabolic endotoxemia by restoring intestinal tight junction protein expression.Lastly, studies in loss-of-function TLR4-mutant mice showed that providing me the opportunity to conduct this research and numerous opportunities to learn new skills and collaborate with other researchers, for encouraging me to challenge myself academically, and for helping me with fellowship applications, abstracts, posters and oral presentations, and manuscript writing throughout the past 4 years of my Ph.D. study.I also would like to sincerely thank to other members of my committee, Dr.
Author: Jinhui Li
Institution: The Ohio State University
Language: English
Topic: Tea Polyphenols and Effects
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2806219980