Nakamura Yasuhiro, Kihara-Negishi Fumiko, Tanigawa Kazunari, Kiriya Mitsuo, Kadowaki Yuki, Imagawa Haruka, Nakanishi Hiroki, Watanabe Shigekazu, Maruyama Keiji, Karasawa Ken
Faculty of Pharma-Sciences, Teikyo University.
Faculty of Medical Technology, Teikyo University.
Biol Pharm Bull. 2023;46(2):257-262. doi: 10.1248/bpb.b22-00666.
Platelet-activating factor acetylhydrolase (PAF-AH) hydrolyzes an acetyl ester at the sn-2 position of platelet-activating factor (PAF), thereby mediating a variety of biological functions. PAF-AH is found in three isoforms: Type I PAF-AH (PAF-AH I) and Type II PAF-AH (PAF-AH II) are intracellular enzymes whereas plasma PAF-AH is characterized by association with lipoprotein in plasma. PAF-AH I forms a tetramer constituted by two catalytic subunits (α1 and α2) with β regulatory subunits. We recently showed that a deficiency of PAF-AH I catalytic subunits in male mice caused an increase of body weight, food intake, and white adipose tissue (WAT) weight. In this study, we examined whether the expression of this enzyme was altered in the differentiation of 3T3-L1 preadipocytes into adipocytes. The amount of PAF-AH I α1 subunit protein was significantly reduced in 3T3-L1 differentiation, while the amount of the PAF-AH I α2 subunit was not changed. Immunoprecipitation analysis of 3T3-L1 differentiation showed that the complex of PAF-AH I catalytic subunits was changed from α1/α2 heterodimer to α2/α2 homodimer. Our findings suggest that changes in PAF-AH I catalytic subunits are involved in adipocyte differentiation of 3T3-L1 and obesity in mice.
血小板活化因子乙酰水解酶（PAF-AH）可水解血小板活化因子（PAF）sn-2位上的乙酰酯，从而介导多种生物学功能。PAF-AH有三种同工型：I型PAF-AH（PAF-AH I）和II型PAF-AH（PAF-AH II）是细胞内酶，而血浆PAF-AH的特征是与血浆中的脂蛋白相关。PAF-AH I形成由两个催化亚基（α1和α2）与β调节亚基构成的四聚体。我们最近发现，雄性小鼠中PAF-AH I催化亚基的缺乏导致体重、食物摄入量和白色脂肪组织（WAT）重量增加。在本研究中，我们检测了该酶的表达在3T3-L1前脂肪细胞分化为脂肪细胞的过程中是否发生改变。在3T3-L1分化过程中，PAF-AH I α1亚基蛋白的量显著减少，而PAF-AH I α2亚基的量未改变。对3T3-L1分化的免疫沉淀分析表明，PAF-AH I催化亚基的复合物从α1/α2异二聚体变为α2/α2同二聚体。我们的研究结果表明，PAF-AH I催化亚基的变化参与了3T3-L1的脂肪细胞分化和小鼠肥胖。
