Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, Chengdu, Sichuan 610000, P.R. China.
Mol Med Rep. 2017 Oct;16(4):5225-5234. doi: 10.3892/mmr.2017.7295. Epub 2017 Aug 21.
Betaine has previously been demonstrated to protect the liver against alcohol‑induced fat accumulation. However, the mechanism through which betaine affects alcohol‑induced hepatic lipid metabolic disorders has not been extensively studied. The present study aimed to investigate the effect of betaine on alcoholic simple fatty liver and hepatic lipid metabolism disorders. A total of 36 rats were randomly divided into control, ethanol and ethanol + betaine groups. Liver function, morphological alterations, lipid content and tumor necrosis factor (TNF)‑α levels were determined. Hepatic expression levels of diacylglycerol acyltransferase (DGAT) 1, DGAT2, sterol regulatory element binding protein (SREBP)‑1c, SREBP‑2, fatty acid synthase (FAS), 3‑hydroxy‑3‑methyl‑glutaryl (HMG)‑CoA reductase, peroxisome proliferator-activated receptor λ coactivator (PGC)‑1α, adiponectin receptor (AdipoR) 1 and AdipoR2 were quantified. Serum and adipose tissue adiponectin levels were assessed using an enzyme‑linked immunoassay. The results demonstrated that alcohol‑induced ultramicrostructural alterations in hepatocytes, including the presence of lipid droplets and swollen mitochondria, were attenuated by betaine. Hepatic triglyceride, free fatty acid, total cholesterol and cholesterol ester contents and the expression of DGAT1, DGAT2, SREBP‑1c, SREBP‑2, FAS and HMG‑CoA reductase were increased following ethanol consumption, however were maintained at control levels following betaine supplementation. Alcohol‑induced decreases in hepatic PGC‑1α mRNA levels and serum and adipose tissue adiponectin concentrations were prevented by betaine. The downregulation of hepatic AdipoR1 which resulted from alcohol exposure was partially attenuated by betaine. No significant differences in liver function, TNF‑α, phospholipid and AdipoR2 levels were observed among the control, ethanol and ethanol + betaine groups. Overall, these results indicated that betaine attenuated the alcoholic simple fatty liver by improving hepatic lipid metabolism via suppression of DGAT1, DGAT2, SREBP‑1c, FAS, SREBP‑2 and HMG‑CoA reductase and upregulation of PGC‑1α.
甜菜碱先前已被证实可防止肝脏脂肪堆积。然而，甜菜碱影响酒精引起的肝脂质代谢紊乱的机制尚未得到广泛研究。本研究旨在探讨甜菜碱对酒精性单纯性脂肪肝和肝脂质代谢紊乱的影响。将 36 只大鼠随机分为对照组、乙醇组和乙醇+甜菜碱组。测定肝功能、形态学改变、脂质含量和肿瘤坏死因子（TNF）-α 水平。检测肝二酰基甘油酰基转移酶（DGAT）1、DGAT2、固醇调节元件结合蛋白（SREBP）-1c、SREBP-2、脂肪酸合成酶（FAS）、3-羟-3-甲基戊二酰基辅酶 A 还原酶、过氧化物酶体增殖物激活受体 λ 共激活因子（PGC）-1α、脂联素受体（AdipoR）1 和 AdipoR2 的表达水平。采用酶联免疫吸附法测定血清和脂肪组织脂联素水平。结果表明，甜菜碱可减轻酒精引起的肝细胞超微结构改变，包括脂滴和肿胀线粒体的存在。肝甘油三酯、游离脂肪酸、总胆固醇和胆固醇酯含量以及 DGAT1、DGAT2、SREBP-1c、SREBP-2、FAS 和 HMG-CoA 还原酶的表达在乙醇摄入后增加，但在甜菜碱补充后维持在对照水平。甜菜碱可防止酒精诱导的肝 PGC-1α mRNA 水平以及血清和脂肪组织脂联素浓度降低。甜菜碱部分减轻了酒精暴露引起的肝 AdipoR1 下调。对照组、乙醇组和乙醇+甜菜碱组的肝功能、TNF-α、磷脂和 AdipoR2 水平无显著差异。综上所述，这些结果表明，甜菜碱通过抑制 DGAT1、DGAT2、SREBP-1c、FAS、SREBP-2 和 HMG-CoA 还原酶以及上调 PGC-1α 来改善肝脂质代谢，从而减轻酒精性单纯性脂肪肝。
