The physiological roles of intracellular lipases in the pathogenesis of nonalcoholic fatty liver diseases

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08985
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: OKAZAKI Sachiko 東京大学, 保健・健康推進本部, 助教 (30648720)
• Co-Investigator(Renkei-kenkyūsha): OKAZAKI Hiroaki 東京大学, 医学部附属病院, 助教 (80610211) ; TAKANASHI Mikio 東京大学, 医学部附属病院, 助教 (70610799) ; TAKASE Satoru 東京大学, 医学部附属病院, 助教 (80508094) ; KUBOTA Midori (20383804) ; TAKAHASHI Masafumi 自治医科大学, 医学部, 教授 (40296108)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: リパーゼ / コレステロール / 非アルコール性脂肪性肝炎

Outline of Final Research Achievements

Accumulating evidence has suggested that hepatic fat accumulation plays a key role in the pathogenesis of nonalcoholic fatty liver diseases (NAFLD) such as hepatitis, liver cirrhosis, and liver cancer. Lipases, which hydrolyze neutral lipids such as triglycerides and esterified cholesterol, may modulate the progression of NAFLD by regulating lipid levels in liver. We found that adenovirus-mediated overexpression of hormone-sensitive lipase (HSL) in diet-induced fatty liver triggers hepatic inflammation, most likely by increasing the levels of free cholesterol in the liver. Overexpression studies using adenovirus carrying other neutral lipases suggested that this response is unique to HSL. Further studies are ongoing in our laboratory to elucidate the underlying molecular mechanisms by using mice deficient in these lipases, which may lead to the identification of a novel therapeutic target for NAFLD.

Free Research Field

医歯薬学