Methyl-donor supplementation in obese mice prevents the progression of NAFLD, activates AMPK and decreases acyl-carnitine levels.
Methyl-donor supplementation in obese mice prevents the progression of NAFLD, activates AMPK and decreases acyl-carnitine levels.
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DOI：
10.1016/j.molmet.2014.04.010
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发表时间：
2014-08
影响因子：
8.1
通讯作者：
Daniel H
中科院分区：
文献类型：
--
作者：
Dahlhoff C;Worsch S;Sailer M;Hummel BA;Fiamoncini J;Uebel K;Obeid R;Scherling C;Geisel J;Bader BL;Daniel H
非酒精性脂肪性肝病（NAFLD）是由肝脏脂质积累增加和脂肪变性引起的，与肝脏一碳（C1）代谢密切相关。我们在C57 BL 6/N小鼠中评估了由高脂肪（HF）饮食诱导的8周以上的NAFLD是否可以通过另外4周的饮食甲基供体补充（MDS）逆转。肥胖小鼠中的MDS未能逆转NAFLD，但阻止了与关键肝脏C1代谢物（例如S-腺苷甲硫氨酸和S-腺苷高半胱氨酸）的主要变化相关的肝脂肪变性的进展。AMPK-α磷酸化水平的增加以及β-HAD活性的增强表明通过脂肪酸氧化途径的通量增加。这得到了伴随的肝脏游离脂肪酸和酰基肉毒碱水平降低的支持。虽然HF饮食改变了肝脏磷脂模式，但MDS没有改变。我们的研究结果表明，膳食甲基供体激活AMPK，这是脂肪酸β-氧化控制中的关键酶，介导脂肪酸利用增加，从而防止肝脏脂质进一步蓄积。
Non-alcoholic fatty liver disease (NAFLD) results from increased hepatic lipid accumulation and steatosis, and is closely linked to liver one-carbon (C1) metabolism. We assessed in C57BL6/N mice whether NAFLD induced by a high-fat (HF) diet over 8 weeks can be reversed by additional 4 weeks of a dietary methyl-donor supplementation (MDS). MDS in the obese mice failed to reverse NAFLD, but prevented the progression of hepatic steatosis associated with major changes in key hepatic C1-metabolites, e.g. S-adenosyl-methionine and S-adenosyl-homocysteine. Increased phosphorylation of AMPK-α together with enhanced β-HAD activity suggested an increased flux through fatty acid oxidation pathways. This was supported by concomitantly decreased hepatic free fatty acid and acyl-carnitines levels. Although HF diet changed the hepatic phospholipid pattern, MDS did not. Our findings suggest that dietary methyl-donors activate AMPK, a key enzyme in fatty acid β-oxidation control, that mediates increased fatty acid utilization and thereby prevents further hepatic lipid accumulation.
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