Elucidation of mechanisms related to toxicity and susceptibility of various fatty acids in NASH pathology

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19340
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Yokohama City University
• Principal Investigator: OGAWA Yuji 横浜市立大学, 医学部, 助教 (20644959)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: lipotoxicity / NAFLD / NASH / palmitate / saturated fatty acid

Outline of Final Research Achievements

In this study, after palmitate-injection, basal diet (BD)-fed mice did not altered the serum ALT, but high fat diet (HFD)-fed mice exhibited increased the serum ALT. Very low dose lipopolysaccharide (LPS)-injection increased the plasma endotoxin on BD-fed mice as same as HFD-fed mice. Both palmitate and very low dose LPS increased ALT on BD-fed mice. On BD-fed mice, palmitate induced inflammatory cells infiltration due to chemokines without ALT elevation and induced mild liver fibrosis via toll like receptor 4 (TLR4) pathway.
Collectively, palmitate alone induced inflammatory cells infiltration and mild liver fibrosis without ALT elevation. Furthermore, palmitate exacerbated NAFLD pathogenesis by cooperative interaction with gut-derived endotoxin. Our results indicate that serum palmitate and plasma gut-derived endotoxin reduction are important for NAFLD treatment.

Free Research Field

NASH/NAFLD