Alternate-day fasting protects the livers of mice against high-fat diet-induced inflammation associated with the suppression of Toll-like receptor 4/nuclear factor κB signaling
Alternate-day fasting protects the livers of mice against high-fat diet-induced inflammation associated with the suppression of Toll-like receptor 4/nuclear factor κB signaling
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DOI：
10.1016/j.nutres.2016.02.001
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发表时间：
2016-06-01
影响因子：
4.5
通讯作者：
Liu, Chao
中科院分区：
文献类型：
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作者：
Yang, Wanwei;Cao, Meng;Liu, Chao
由于不健康的生活方式，大量人群患有肝脏脂质堆积和非酒精性脂肪性肝炎。能量限制（ER）是预防慢性疾病的有效营养干预措施。然而，连续 ER 的依从性差限制了其有效性。作为每日 ER 的替代方案，隔日禁食 (ADF) 可能更有效。我们假设 ADF 可以改善肥胖、高血糖和胰岛素抵抗，并保护肝脏免受高脂饮食 (HFD) 诱导的脂肪变性和炎症的影响。在本研究中，我们使用 C57BL/6 小鼠来测试 ADF 的有益效果。将 30 只雄性 6 周龄 C57BL/6 小鼠分为 3 组（每组 10 只，总 N = 30）：第 1 组饲喂普通饲料，第 2 组随意饲喂 HFD，第 3 组接受 ADF。第三组的小鼠每隔一天随意喂食HFD，并于第二天禁食。 12 个月后，与持续 HFD 喂养的小鼠相比，接受 ADF 喂养的小鼠体重和空腹血糖水平降低，胰岛素抵抗和肝脂肪变性得到改善。此外，ADF组小鼠血清转氨酶水平低于HFD组。此外，ADF方案抑制了肝脏中Toll样受体4和核因子κB蛋白的表达水平，并抑制了炎症通路基因白细胞介素1β、肿瘤坏死因子α和血清淀粉样蛋白A。这些发现表明，长期ADF可以保护小鼠肝脏免受HFD诱导的肝脂肪变性和与Toll样受体4/核因子κB信号抑制相关的肝细胞损伤。 (C) 2016 Elsevier Inc. 保留所有权利。
Because of unhealthy lifestyles, a large number of people are suffering from hepatic lipid accumulation and nonalcoholic steatohepatitis. Energy restriction (ER) is an effective nutritional intervention for preventing chronic disease. However, poor compliance with continuous ER limits its effectiveness. As an alternative to daily ER, alternate-day fasting (ADF) may be more effective. We hypothesized that ADF would improve obesity, hyperglycemia, and insulin resistance and protect the liver against high-fat diet (HFD)-induced steatosis and inflammation. In this study, we used C57BL/6 mice to test the beneficial effects of ADF. Thirty male 6-week-old C57BL/6 mice were divided into 3 groups (10 per group, total N = 30): 1 group was fed chow diet, the second was fed HFD ad libitum, and the third group was submitted to ADF. The mice in the third group were fed the HFD ad libitum every other day and fasted the following day. After 12 months, the mice submitted to ADF exhibited reduced body weights and fasting glucose levels and improved insulin resistance and hepatic steatosis compared with continuous HFD-fed mice. In addition, the serum transaminase levels in the mice of the ADF group were lower than those of the HFD group. Moreover, the ADF regimen suppressed the expression levels of Toll-like receptor 4 and nuclear factor kappa B protein in the liver and suppressed the inflammatory pathway genes interleukin 1 beta, tumor necrosis factor alpha, and serum amyloid A. These finding indicate that long-term ADF protects mouse livers against HFD-induced hepatic steatosis and hepatocellular damage associated with the suppression of Toll-like receptor 4/nuclear factor kappa B signaling. (C) 2016 Elsevier Inc. All rights reserved.