Department of Physiology, Faculty of Pharmacy, Seville University, 41012 Seville, Spain.
Food Funct. 2021 Apr 7;12(7):3022-3032. doi: 10.1039/d0fo02831b. Epub 2021 Mar 12.
Binge drinking (BD) is the main alcohol consumption pattern among teenagers. Recently, oxidative stress (OS) generated by BD exposure has been related to hepatic metabolic deregulation and cardiovascular dysfunction. This study analyzed if BD by generating oxidative stress modulates the alteration in hepatic energy homeostasis through two important regulators of energy metabolism: the NAD-dependent sirtuin deacetylase (SIRT1) and AMP-activated protein kinase (AMPK) and if supplementation with the antioxidant selenium (Se) improves these metabolic disorders. Four groups of adolescent rats supplemented or not with Se (0.4 ppm) and exposed to intermittent i.p. BD were used. BD rats showed an increased AST/ALT ratio, total bilirubin in serum and lipid peroxidation in the liver. The BD rats also showed a higher abdominal/thoracic ratio and increased levels of TG, gluc, and chol compared to the control group, provoking an increase in mean blood pressure (MBP). This alcohol consumption pattern decreased hepatic Se deposits, cytoplasmic GPx activity, and GSH levels as well as the expressions of two metabolic sensors and the pAMPK/AMPK ratio. Se supplementation restored antioxidant parameters and decreased lipid oxidation, avoiding OS and improving the hepatic expression of pAMPK and SIRT1, contributing to the improvement of metabolic (better lipid profile and IRS-1 expression) and vascular function (lower MBP), and to the increase of hepatic functionality (lower AST/ALT ratio). All these actions decrease cardiometabolic risk factor development in the short and long term and could disrupt the relationship between BD and MS, two problems which are currently affecting adolescents.
binge drinking (BD) 是青少年主要的饮酒模式。最近,BD 暴露引起的氧化应激 (OS) 与肝代谢失调和心血管功能障碍有关。本研究分析了通过产生氧化应激,BD 是否通过两种重要的能量代谢调节剂来调节肝能量稳态的改变:NAD 依赖性组蛋白去乙酰化酶 (SIRT1) 和 AMP 激活的蛋白激酶 (AMPK),以及抗氧化剂硒 (Se) 的补充是否可以改善这些代谢紊乱。使用了四组补充或不补充 Se(0.4ppm)并间歇性腹腔注射 BD 的青少年大鼠。BD 大鼠表现出 AST/ALT 比值升高、血清总胆红素和肝脂质过氧化增加。BD 大鼠还表现出更高的腹部/胸部比值以及更高的 TG、葡萄糖和胆固醇水平,导致平均血压 (MBP) 升高。这种饮酒模式降低了肝硒沉积、细胞质 GPx 活性和 GSH 水平以及两种代谢传感器的表达和 pAMPK/AMPK 比值。Se 补充恢复了抗氧化参数,减少了脂质氧化,避免了 OS 并改善了肝 pAMPK 和 SIRT1 的表达,有助于改善代谢(更好的脂质谱和 IRS-1 表达)和血管功能(更低的 MBP),并增加肝功能(更低的 AST/ALT 比值)。所有这些作用都降低了短期和长期的心血管代谢风险因素的发展,并可能破坏 BD 和 MS 之间的关系,这两个问题目前都在影响青少年。