Reversal of high-fat diet-induced hepatic steatosis by n-3 LCPUFA: role of PPAR-α and SREBP-1c
Reversal of high-fat diet-induced hepatic steatosis by n-3 LCPUFA: role of PPAR-α and SREBP-1c
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DOI：
10.1016/j.jnutbio.2014.04.011
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发表时间：
2014-09-01
影响因子：
5.6
通讯作者：
D'Espessailles, Amanda
中科院分区：
文献类型：
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作者：
Dossi, Camila G.;Tapia, Gladys S.;D'Espessailles, Amanda
非酒精性脂肪性肝病的特征是在没有大量饮酒的情况下，三酰甘油在肝脏中异常堆积。在这些条件下，已经观察到肝脏n-3长链多不饱和脂肪酸(LCPUFAs)的生物利用度受到损害。本研究的目的是通过改变正常热量饮食和补充n-3LCPUFA来测试高脂饮食(HFD)对小鼠肝脏的促骨化和促炎作用的逆转作用。雄性C57BL/6J小鼠分别给予对照饲料(CD)和高脂饲料(HFD)12周。将对照组和HFD组分为两组，分别给予Cd或Cd加n-3LCPUFA治疗8周。此后，取血和肝样本，分析代谢、形态、氧化应激、炎症和信号参数。与仅将高脂膳食转变为等热量饮食相比，补充n-3LCPUFA的高脂饮食改变显著降低了胰岛素抵抗和肝脏脂肪变性。此外，n-3LCPUFA可抑制HFD诱导的肥胖、脂肪细胞增大、肝脏氧化应激和炎性细胞因子表达的增加，以控制值。重要的是，补充n-3LCPUFA可消除HFD诱导的肝脏SREBP-1c/PPAR-α比率的增加，这表明肝脏的代谢状态从造脂状态转变为有利于脂肪酸氧化和脂肪变性减轻的状态。这些发现可能为在肝脏脂肪变性患者中使用常热量饮食加n-3LCPUFA提供合理的依据。(C)2014 Elsevier Inc.保留所有权利。
Nonalcoholic fatty liver disease is characterized by an abnormal accumulation of triacylglycerides in the liver in absence of significant alcohol consumption. Under these conditions, it has been observed an impaired bioavailability of hepatic n-3 long-chain polyunsaturated fatty acids (LCPUFAs). The aim of this study was to test the reversion of the prosteatotic and proinflammatory effects of high-fat diet (HFD) in the mouse liver by changing to normocaloric diet and n-3 LCPUFA supplementation. Male C57BL/6J mice were given either control diet (CD) or HFD for 12 weeks. Control and HFD groups were divided into subgroups that continue with CD or subjected to CD plus n-3 LCPUFA for 8 additional weeks. After this time, blood and liver samples were taken and metabolic, morphologic, oxidative stress, inflammatory and signaling parameters were analyzed. The dietary change from HFD to a normocaloric diet with n-3 LCPUFA supplementation significantly reduced insulin resistance and liver steatosis when compared to switching HFD to normocaloric diet alone. In addition, HFD-induced increases in adiposity, adipocyte enlargement and liver oxidative stress and inflammatory cytokine expression were suppressed by n-3 LCPUFA to control values. Importantly, n-3 LCPUFA supplementation abolish HFD-induced enhancement in hepatic SREBP-1c/PPAR-alpha ratios, suggesting a change in the metabolic status of the liver from a lipogenic condition to one favoring fatty acid oxidation and steatosis attenuation. These findings may provide the rational basis for the use of normocaloric diets supplemented with n-3 LCPUFA in patients with liver steatosis. (C) 2014 Elsevier Inc. All rights reserved.