Okmeydanı Training and Research Hospital, Internal Medicine Department, Istanbul, Turkey.
Okmeydanı Training and Research Hospital, Medical Biochemistry Department, Istanbul, Turkey.
Cytokine. 2018 Nov;111:496-499. doi: 10.1016/j.cyto.2018.05.030. Epub 2018 Jun 14.
Angiopoietin-like peptide 4 (ANGPTL-4) plays an important role in lipid metabolism by inhibiting the enzyme lipoprotein lipase. This effect of ANGPTL-4 results in suppression of the release of plasma triglyceride-derived fatty acids. Increase in fatty acid levels entering to the liver and abnormalities in their secretion is one of the main mechanisms in pathogenesis of hepatic steatosis. In this study, we aimed to investigate the role of ANGPTL-4 in pathogenesis of hepatic steatosis by determining its levels in patients with fatty liver disease.
Totally 51 patients (age: 37.9 ± 9.9 years, M/F) diagnosed with grade 2-3 hepatic steatosis with ultrasound and 30 healthy volunteers (age: 34.8 ± 9.5 years, M/F) were included in the study. In both groups, routine biochemical tests including fasting blood glucose, fasting insulin levels, triglyceride, total cholesterol, LDL- cholesterol, HDL-cholesterol, AST, ALT, ALP, GGT levels were measured together with the ANGPTL-4 levels. In determination of ANGPTL-4 levels, ELISA was performed.
When compared with the control group, ANGPTL-4 levels were determined to be decreased in patients with hepatic steatosis (369 ± 243 vs 303 ± 286 ng/mL, p = 0.014). There was a negative weak correlation observed between ANGPTL-4 and triglyceride levels (r = -0.246, p = 0.027). Among all groups, when patients with and without insulin resistance were compared; ANGPTL-4 levels were determined to be similar. While fasting blood glucose levels were similar between 2 groups; fasting insulin and triglyceride levels were determined to be increased in hepatic steatosis group (Insulin 17.7 ± 12 vs 7.4 ± 3.3 µIU/mL, p < 0.001, triglyceride 158 ± 46.4 vs 118 ± 59.8 mg/dL p < 0.001).
We have determined lower serum ANGPTL-4 levels in patients with hepatic steatosis. ANGPTL-4 that is regulating LPL activity plays an important role in fatty liver disease pathogenesis via free fatty acid metabolism and peroxisome proliferator-activated receptor-delta (PPAR-δ). We believe that the results of this study would elucidate the investigations about the mechanism of fatty liver disease development and treatments targeting ANGPTL-4.
血管生成素样肽 4（ANGPTL-4）通过抑制脂蛋白脂肪酶来发挥重要的脂质代谢作用。ANGPTL-4 的这种作用导致血浆甘油三酯衍生的脂肪酸释放受到抑制。进入肝脏的脂肪酸水平增加和其分泌异常是肝脂肪变性发病机制的主要机制之一。在这项研究中，我们通过测定脂肪性肝病患者的 ANGPTL-4 水平来研究 ANGPTL-4 在肝脂肪变性发病机制中的作用。
共纳入 51 名（年龄：37.9±9.9 岁，男/女）经超声诊断为 2-3 级肝脂肪变性的患者和 30 名健康志愿者（年龄：34.8±9.5 岁，男/女）。在两组中，均同时测定常规生化检测包括空腹血糖、空腹胰岛素水平、甘油三酯、总胆固醇、LDL-胆固醇、HDL-胆固醇、AST、ALT、碱性磷酸酶、γ-谷氨酰转移酶水平和 ANGPTL-4 水平。测定 ANGPTL-4 水平采用 ELISA 法。
与对照组相比，肝脂肪变性患者的 ANGPTL-4 水平降低（369±243 与 303±286ng/mL，p=0.014）。ANGPTL-4 与甘油三酯水平之间存在弱负相关（r=-0.246，p=0.027）。在所有组中，比较有和无胰岛素抵抗的患者时，发现 ANGPTL-4 水平相似。两组的空腹血糖水平相似，但肝脂肪变性组的空腹胰岛素和甘油三酯水平升高（胰岛素 17.7±12 与 7.4±3.3µIU/mL，p<0.001，甘油三酯 158±46.4 与 118±59.8mg/dL，p<0.001）。
我们发现肝脂肪变性患者血清 ANGPTL-4 水平较低。ANGPTL-4 通过调节 LPL 活性，通过游离脂肪酸代谢和过氧化物酶体增殖物激活受体-δ（PPAR-δ）在脂肪性肝病发病机制中发挥重要作用。我们相信，这项研究的结果将阐明关于脂肪性肝病发展和针对 ANGPTL-4 的治疗的机制研究。
