Triscari J, Sullivan A C
Int J Obes. 1984;8 Suppl 1:227-39.
A novel anti-obesity agent which inhibits fatty acid synthesis and stimulates fatty acid oxidation is described. The hydrochloride salt of Ro 22-0654 (4-amino-5-ethyl-3-thiophenecarboxylic acid methyl ester) is a potent inhibitor of fatty acid and cholesterol synthesis in rat-isolated hepatocytes. Hepatic fatty acid synthesis was inhibited in vivo in a dose-dependent fashion with a duration of action of approximately 8 h. Adipose tissue fatty acid synthesis was also inhibited in vivo. Inhibition of fatty acid synthesis occurs without any apparent effect on several lipogenic enzymes, the tricarboxylic acid cycle, and the pentose phosphate shunt. Ro 22-0654 also stimulated fatty acid oxidation (in vitro) and lipolysis (in vivo). In long-term studies (2 months), Ro 22-0654 decreased body weight gain in Sprague Dawley and genetically-obese Zucker rats. Food intake was decreased following a single dose and for several days during chronic treatment. However, while food intake quickly returned to normal, body weight gain remained lower in treated rats. The effect on body weight gain can be ascribed to decreased total body lipid content in the absence of an effect on lean body mass. It is suggested that Ro 22-0654 may have utility in the treatment of human obesity.
描述了一种新型抗肥胖剂，它可抑制脂肪酸合成并刺激脂肪酸氧化。Ro 22-0654（4-氨基-5-乙基-3-噻吩羧酸甲酯）的盐酸盐是大鼠分离肝细胞中脂肪酸和胆固醇合成的有效抑制剂。肝脂肪酸合成在体内呈剂量依赖性抑制，作用持续时间约为8小时。体内脂肪组织脂肪酸合成也受到抑制。脂肪酸合成的抑制在对几种生脂酶、三羧酸循环和磷酸戊糖途径没有任何明显影响的情况下发生。Ro 22-0654还刺激脂肪酸氧化（体外）和脂解作用（体内）。在长期研究（2个月）中，Ro 22-0654降低了斯普拉格·道利大鼠和遗传性肥胖的 Zucker 大鼠的体重增加。单次给药后以及慢性治疗期间的几天内食物摄入量减少。然而，虽然食物摄入量很快恢复正常，但治疗组大鼠的体重增加仍然较低。体重增加的影响可归因于总体脂含量的降低，而对瘦体重没有影响。提示Ro 22-0654可能对治疗人类肥胖有用。
