Excessive ingestion of sugar causes the abnomality of endoplasmic reticulum, resulting in providing for NASH

2016 Fiscal Year Final Research Report

• Project/Area Number: 16K12742
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Eating habits
• Research Institution: Kanazawa Medical University
• Principal Investigator: UEDA Tadashi 金沢医科大学, 総合医学研究所, 助教 (80151794)
• Research Collaborator: TAKEUCHI Masayoshi 金沢医科大学, 総合医学研究所, 教授 (20154982) ; TAKATA Takanobu 金沢医科大学, 総合医学研究所, 助教 (20515308)
• Project Period (FY): 2016-04-01 – 2017-03-31
• Keywords: 終末糖化タンパク / グリセルアルデヒド / 初代培養心筋細胞 / 初代培養肝細胞 / 小胞体ストレス / NASH / オートファジー / 電子顕微鏡

Outline of Final Research Achievements

It is suggested that glyceraldehyde-derived advanced glycation products (GA-AGEs) play a key role in various diseases. We examined the effect of GA, which is a precursor of GA-AGEs, at concentrations between 0-4 mM during a period of 24 h in the primary cultured cardiomyocytes and hepatocytes. Both cultured cells were affected severely by GA, and endoplasmic reticulum (ER) was the target organelle, and thereafter mitochondria(Mt) were disrupted. Cultured hepatocytes appeared with the characteristics similar to NASH, which contained numerous lipid droplets and vacuoles. The cells which were affected by ER stress suppressed autophagy. Numerous hepatocytes in NASH model mice appeared positive against anti-TAGE antibody. Moreover, they showed ballooning cells, and ER and Mt were collapsed.
These results suggested that accumulated TAGE may cause NASH and ER plays a key role of induction into NASH.

Free Research Field

解剖学