Function of primary fatty acid amides as lipid mediators

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21285
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 38:Agricultural chemistry and related fields
• Research Institution: Osaka Metropolitan University (2022); Osaka Prefecture University (2020-2021)
• Principal Investigator: Yamaji Ryoichi 大阪公立大学, 大学院農学研究科, 教授 (00244666)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: 脂肪酸アミド / オレアミド / 骨格筋 / 小腸 / リンパ管 / 門脈 / 脂肪酸アミド加水分解酵素

Outline of Final Research Achievements

In this study, we obtained information on the molecular mechanism by which oleamide, a primary fatty acid amide, induces muscle hypertrophy in the physiological concentration range, and investigated the absorption mechanism, the accumulation tissues, and the action there of oleamide. Oleamide suppressed muscle atrophy by activating mTOR signaling via cannabinoid receptor 1. Furthermore, oleamide was taken up by intestinal epithelial cells via CD36, a long-chain fatty acid transporter, and metabolized intracellularly by fatty acid amide hydrolase. Oleamide that escaped metabolism bound to albumin and was transported from the small intestine to the whole body via the portal vein route. Oleamide accumulated in white adipose tissue, inhibited the expression of inflammation-related factors, and reduced abdominal white fat mass.

Free Research Field

栄養生化学

Academic Significance and Societal Importance of the Research Achievements

オレアミドの血中濃度は100ー1000 nMであるのに対して、in vitro 研究では数10 μMレベル（例えば抗炎症効果は50 μM以上）で機能が評価されており、これらの濃度のギャップが脂質研究での一級脂肪酸アミドの質の学術的発展を停滞させてきた。しかし本研究成果は、オレアミドが体外から体内に取り込まれる際に大半が小腸上皮細胞内で代謝されることを示し、また代謝を回避したオレアミドが蓄積する組織とそこでの機能を明らかにすることを証明し、生化学・栄養化学の脂質分野におけるオレアミドの新規の概念を提言する学術的意義を持つ。