Betaine improves nonalcoholic fatty liver and associated hepatic insulin resistance: a potential mechanism for hepatoprotection by betaine
Betaine improves nonalcoholic fatty liver and associated hepatic insulin resistance: a potential mechanism for hepatoprotection by betaine
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DOI：
10.1152/ajpgi.00249.2010
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发表时间：
2010-11-01
影响因子：
4.5
通讯作者：
Morgan, Timothy R.
中科院分区：
文献类型：
--
作者：
Kathirvel, Elango;Morgan, Kengathevy;Morgan, Timothy R.
Kathirvel E，Morgan K，Nandgiri G，桑多瓦尔BC，Caudill MA，Bottiglieri T，French SW，Morgan TR.甜菜碱改善非酒精性脂肪肝和相关的肝脏胰岛素抵抗：甜菜碱保肝作用的潜在机制。美国生理学杂志胃肠和肝脏生理学299：G1068-G1077，2010。首次发表于2010年8月19日; doi：10.1152/ajpgi.00249.2010.-非酒精性脂肪肝（NAFL）是一种常见的肝脏疾病，与胰岛素抵抗有关。甜菜碱已经在动物模型和小型临床试验中被测试为NAFL的治疗方法，结果好坏参半。本研究旨在确定甜菜碱治疗是否会预防或治疗小鼠NAFL，并了解甜菜碱如何逆转肝脏胰岛素抵抗。给雄性小鼠喂食含有20%来自脂肪的热量的中等高脂肪饮食（mHF）7个月（mHF）或8个月（mHF 8），不含甜菜碱，含甜菜碱（mHFB），或最后6周含甜菜碱（mHF 8B）。对照小鼠喂食含有9%脂肪热量的标准食物7个月（SF）或8个月（SF 8）。使HepG 2细胞产生胰岛素抵抗，然后在有或没有甜菜碱的情况下进行研究。与SF小鼠相比，mHF小鼠的体重、空腹血糖、胰岛素和甘油三酯较高，肝脏脂肪较多。甜菜碱降低空腹血糖、胰岛素、甘油三酯和肝脂肪。在mHF 8B组中，甜菜碱治疗显著改善胰岛素抵抗和肝脂肪变性。肝脏甜菜碱含量在mHF中显著降低，在mHFB中显著升高。甜菜碱治疗逆转了mHF和胰岛素抵抗HepG 2细胞中肝脏胰岛素信号传导的抑制，包括胰岛素受体底物1（IRS 1）磷酸化和糖原合成的下游信号传导途径的正常化。甜菜碱治疗可预防和治疗NAFL小鼠中度高膳食脂肪模型中的脂肪肝。甜菜碱还通过增加IRS 1的活化部分逆转肝脏胰岛素抵抗，从而改善下游信号传导途径。
Kathirvel E, Morgan K, Nandgiri G, Sandoval BC, Caudill MA, Bottiglieri T, French SW, Morgan TR. Betaine improves nonalcoholic fatty liver and associated hepatic insulin resistance: a potential mechanism for hepatoprotection by betaine. Am J Physiol Gastrointest Liver Physiol 299: G1068-G1077, 2010. First published August 19, 2010; doi: 10.1152/ajpgi.00249.2010.-Nonalcoholic fatty liver (NAFL) is a common liver disease, associated with insulin resistance. Betaine has been tested as a treatment for NAFL in animal models and in small clinical trials, with mixed results. The present study aims to determine whether betaine treatment would prevent or treat NAFL in mice and to understand how betaine reverses hepatic insulin resistance. Male mice were fed a moderate high-fat diet (mHF) containing 20% of calories from fat for 7 (mHF) or 8 (mHF8) mo without betaine, with betaine (mHFB), or with betaine for the last 6 wk (mHF8B). Control mice were fed standard chow containing 9% of calories from fat for 7 mo (SF) or 8 mo (SF8). HepG2 cells were made insulin resistant and then studied with or without betaine. mHF mice had higher body weight, fasting glucose, insulin, and triglycerides and greater hepatic fat than SF mice. Betaine reduced fasting glucose, insulin, triglycerides, and hepatic fat. In the mHF8B group, betaine treatment significantly improved insulin resistance and hepatic steatosis. Hepatic betaine content significantly decreased in mHF and increased significantly in mHFB. Betaine treatment reversed the inhibition of hepatic insulin signaling in mHF and in insulin-resistant HepG2 cells, including normalization of insulin receptor substrate 1 (IRS1) phosphorylation and of downstream signaling pathways for gluconeogenesis and glycogen synthesis. Betaine treatment prevents and treats fatty liver in a moderate high-dietary-fat model of NAFL in mice. Betaine also reverses hepatic insulin resistance in part by increasing the activation of IRS1, with resultant improvement in downstream signaling pathways.