<title_ja>リゾリン脂質アシル転移酵素LPLAT10/LPCAT4/LPEAT2の肝臓特異的な高発現は、グルコース依存性インスリン分泌を促進する</title_ja> <title_en>Liver-specific LPLAT10/LPCAT4/LPEAT2 overexpression increases glucose-stimulated insulin secretion</title

2-B-P-060 <title_ja>リゾリン脂質アシル転移酵素LPLAT10/LPCAT4/LPEAT2の肝臓特異的な高発現は、グルコース依存性インスリン分泌を促進する</title_ja> <title_en>Liver-specific LPLAT10/LPCAT4/LPEAT2 overexpression increases glucose-stimulated insulin secretion</title_en> 〇清水かほり¹、小野萌¹、三家本武成¹、裏山悠哉¹、中西広樹²、道永昌太郎³、吉田瀬七¹、岩崎美穂¹、寺田知行¹、櫻井文教⁴、水口裕之^4,5,6,7,8、進藤英雄^9,10、冨田晃司¹、西中徹¹ Kahori Shimizu¹, Moe Ono¹, Takenari Mikamoto¹, Yuya Urayama¹, Hiroki Nakanishi², Shotaro Michinaga³, Sena Yoshida¹, Miho Iwasaki¹, Tomoyuki Terada¹, Fuminori Sakurai⁴, Hiroyuki Mizuguchi^4,5,6,7,8, Hideo Shindou^9,10, Koji Tomita¹, Toru Nishinaka¹ ¹大阪大谷大・薬、²（株）リピドームラボ、³明治薬科大・薬、⁴大阪大・院薬、⁵医薬基盤・健康・栄養研、⁶大阪大・国際医工セ、⁷大阪大・先導、⁸大阪大・感染症総合教育研究拠点、⁹国立国際医療研究セ、¹⁰東京大・院医 ¹Pharm., Osaka Ohtani Univ., ²Lipidome Lab Co., Ltd., ³Meiji Pharm. Univ., ⁴Grad. Sch. of Pharma. Sci., Osaka Univ., ⁵Natl. Inst. of Biomed. Innov. Health Nutr., ⁶MEIC, Osaka Univ., ⁷OTRI, Osaka Univ., ⁸CiDER, Osaka Univ., ⁹NCGM, ¹⁰Univ. of Tokyo Type 2 diabetes mellitus (T2DM) incidence is increasing worldwide. The fatty acid composition of phospholipids—a major component of biological membranes—has received research attention owing to their involvement in T2DM onset and progression. We hypothesized that changes in the fatty acid composition of phospholipids in the liver, the central organ of energy metabolism, alleviate their aberrant metabolism. We focused on lysophospholipid acyltransferase 10 (LPLAT10/LPCAT4/LPEAT2), an enzyme that changes the fatty acid composition of phospholipids, and examined the effect of LPLAT10 on glucose metabolism. To overexpress LPLAT10 in mouse liver, we generated an LPLAT10-expressing adenovirus (Ad) vector (Ad-LPLAT10) using an improved Ad vector. Hepatic LPLAT10 mRNA and protein expression in Ad-LPLAT10-treated mice was much higher than that in mice treated with control Ad vector. Induction of glucose-stimulated insulin secretion (GSIS) suppressed postprandial hyperglycemia in Ad-LPLAT10-treated mice compared with that in control Ad-vector-treated mice. Hepatic and serum levels of phosphatidylcholine, containing polyunsaturated fatty acid, were elevated in Ad-LPLAT10-treated mice. Elevated phosphatidylcholine levels increased GSIS in mouse insulinoma cells. Our study suggests that LPLAT10 is a promising new therapeutic target for T2DM.