Zagayko A L, Shkapo A I, Fylymonenko V P, Briukhanova T O
Ukr Biochem J. 2016 May-Jun;88(3):78-82. doi: 10.15407/ubj88.03.078.
The syndrome of insulin resistance (IR) is one of the leading reasons for the increased risk of cardiovascular diseases and their complications. Among the key components of IR are obesity and dyslipidemia. Hydroxycitric acid (HCA), an inhibitor of a key enzyme of lipogenesis ATP citrate lyase (ACLY) is a promising obesity treatment agent. The aim of this work was to investigate the effect of HCA on lipid and lipoproteins content in the blood serum, as well as lipid content and activity of some lipid metabolism enzymes in the liver of hamsters with IR. IR was modeled by keeping animals on high-fat diet with addition of fructose. Lipid content was determined by using standard reagent kits, the level of lipoproteins, the activity of glucose 6-phosphate dehydrogenase and ACLY – spectrophotometrically, lysosomal lipase activity – fluorimetrically. Development of hyperlipidemia and atherogenic dyslipidemia, lipid accumulation in the liver, activation of lysosomal lipase and ACLY and reduction of glucose 6-phosphate dehydrogenase activity were shown under IR. The treatment by HCA reduces the manifestations of hyperlipidemia, but enhances the lipid accumulation in the liver.
胰岛素抵抗(IR)综合征是心血管疾病及其并发症风险增加的主要原因之一。IR的关键组成部分包括肥胖和血脂异常。羟基柠檬酸(HCA)是脂肪生成关键酶ATP柠檬酸裂解酶(ACLY)的抑制剂,是一种有前景的肥胖治疗药物。这项工作的目的是研究HCA对IR仓鼠血清中脂质和脂蛋白含量以及肝脏中一些脂质代谢酶的脂质含量和活性的影响。通过给动物喂食添加果糖的高脂饮食来模拟IR。使用标准试剂盒测定脂质含量,用分光光度法测定脂蛋白水平、葡萄糖6-磷酸脱氢酶和ACLY的活性,用荧光法测定溶酶体脂肪酶活性。在IR条件下,出现了高脂血症和致动脉粥样硬化性血脂异常、肝脏脂质蓄积、溶酶体脂肪酶和ACLY激活以及葡萄糖6-磷酸脱氢酶活性降低。HCA治疗可减轻高脂血症的表现,但会增强肝脏中的脂质蓄积。