白色脂肪组织中不对称二甲基精氨酸相关酶的活性与循环脂质生物标志物有关。
Activities of asymmetric dimethylarginine-related enzymes in white adipose tissue are associated with circulating lipid biomarkers.
机构信息
Department of Internal Medicine, Division of Endocrinology and Metabolism, Toshiba Rinkan Hospital, 7-9-1 Kami-tsuruma, Minami-ku, Sagamihara, Kanagawa, 252-0385, Japan.
出版信息
Diabetol Metab Syndr. 2012 Apr 30;4(1):17. doi: 10.1186/1758-5996-4-17.
BACKGROUND
Asymmetric NG,NG-dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is regulated by the enzymatic participants of synthetic and metabolic processes, i.e., type I protein N-arginine methyltransferase (PRMT) and dimethylarginine dimethylaminohydrolase (DDAH). Previous reports have demonstrated that circulating ADMA levels can vary in patients with type 1 and type 2 diabetes mellitus (T2DM). White adipose tissue expresses the full enzymatic machinery necessary for ADMA production and metabolism; however, modulation of the activities of adipose ADMA-related enzymes in T2DM remains to be determined.
METHODS
A rodent model of T2DM using 11- and 20-week old Goto-Kakizaki (GK) rats was used. The expression and catalytic activity of PRMT1 and DDAH1 and 2 in the white adipose tissues (periepididymal, visceral and subcutaneous fats) and femur skeletal muscle tissue were determined by immunoblotting, in vitro methyltransferase and in vitro citrulline assays.
RESULTS
Non-obese diabetic GK rats showed low expression and activity of adipose PRMT1 compared to age-matched Wistar controls. Adipose tissues from the periepididymal, visceral and subcutaneous fats of GK rats had high DDAH1 expression and total DDAH activity, whereas the DDAH2 expression was lowered below the control value. This dynamic of ADMA-related enzymes in white adipose tissues was distinct from that of skeletal muscle tissue. GK rats had lower levels of serum non-esterified fatty acids (NEFA) and triglycerides (TG) than the control rats. In all subjects the adipose PRMT1 and DDAH activities were statistically correlated with the levels of serum NEFA and TG.
CONCLUSION
Activities of PRMT1 and DDAH in white adipose tissues were altered in diabetic GK rats in an organ-specific manner, which was reflected in the serum levels of NEFA and TG. Changes in adipose ADMA-related enzymes might play a part in the function of white adipose tissue.
背景
非对称 NG、NG-二甲基精氨酸（ADMA）是一氧化氮合酶的内源性抑制剂，受合成和代谢过程的酶类参与者调节，即 I 型蛋白 N-精氨酸甲基转移酶（PRMT）和二甲基精氨酸二甲氨基水解酶（DDAH）。先前的报告表明，1 型和 2 型糖尿病（T2DM）患者的循环 ADMA 水平可能有所不同。白色脂肪组织表达产生和代谢 ADMA 所需的完整酶机制；然而，T2DM 中脂肪 ADMA 相关酶的活性调节仍有待确定。
方法
使用 11 周和 20 周大的 Goto-Kakizaki（GK）大鼠建立 T2DM 啮齿动物模型。通过免疫印迹、体外甲基转移酶和体外瓜氨酸测定法测定白色脂肪组织（附睾、内脏和皮下脂肪）和股骨骨骼肌组织中 PRMT1 和 DDAH1 和 2 的表达和催化活性。
结果
与年龄匹配的 Wistar 对照相比，非肥胖型糖尿病 GK 大鼠的脂肪 PRMT1 表达和活性较低。GK 大鼠附睾、内脏和皮下脂肪的脂肪组织具有高 DDAH1 表达和总 DDAH 活性，而 DDAH2 表达低于对照值。白色脂肪组织中 ADMA 相关酶的这种动态与骨骼肌组织不同。GK 大鼠的血清非酯化脂肪酸（NEFA）和甘油三酯（TG）水平低于对照大鼠。在所有受试者中，脂肪 PRMT1 和 DDAH 活性与血清 NEFA 和 TG 水平呈统计学相关。
结论
糖尿病 GK 大鼠白色脂肪组织中 PRMT1 和 DDAH 的活性发生了器官特异性改变，这反映在血清 NEFA 和 TG 水平上。脂肪 ADMA 相关酶的变化可能在白色脂肪组织的功能中起作用。
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