Effect of dietary lipid composition on trans-intestinal cholesterol excretion

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K11115
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Kindai University
• Principal Investigator: KAMISAKO Toshinori 近畿大学, 大学病院, 教授 (20233934)
• Co-Investigator(Kenkyū-buntansha): 田中 裕滋 近畿大学, 大学病院, 講師 (00465650)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 経小腸コレステロール排泄 / 魚油 / エゼチミブ

Outline of Final Research Achievements

Small intestine has a pathway for the excretion of cholesterol from blood into the lumen (TICE). In the present study, we investigated whether the TICE is involved in the cholesterol-lowering effects of fish oil and ezetimibe, in rodent. Fish oil increased faecal cholesterol excretion by 41%, and increased the expression of Abcg5/g8 in the small intestine, which is thought to be associated with faecal cholesterol excretion, suggesting that fish oil may be associated with TICE. Ezetimibe did not increase intestinal Abcg5/g8 expression or faecal cholesterol excretion, but increase hepatic Abcg5/g8 expression. The combination of fish oil and ezetimibe markedly improved fatty liver. The improvement was associated with increased hepatic Abcg5/g8 and Mdr2 expression. These results suggest that fish oil promotes TICE and ezetimibe promotes cholesterol excretion from the liver into bile. The combination was efficient for the reduction of hepatic lipid.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

非アルコール性脂肪性肝疾患（NAFLD）は非飲酒者におけるメタボリック症候群の肝臓における表現型であり、我が国においては増加傾向にある。またNAFLDの20％では非アルコール性脂肪性肝炎（NASH）を引き起こし5年の経過観察で10～25％が肝硬変に進行する。さらにNASH肝硬変では肝細胞癌が5年で10％発生することから、NAFLDに対しては、食事や運動に加え、積極的なNAFLDの治療が注目されている。本研究における成果は食事中のω３脂肪酸含有量がエゼチミブの脂質改善作用に影響を及ぼし、魚油とエゼチミブの併用がNAFLDの治療に有効であることが示唆された。