The Ameliorating Effects of Apple Polyphenol Extract on High-Fat-Diet-Induced Hepatic Steatosis Are SIRT1-Dependent: Evidence from Hepatic-Specific SIRT1 Heterozygous Mutant C57BL/6 Mice,Journal of Agricultural and Food Chemistry

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The Ameliorating Effects of Apple Polyphenol Extract on High-Fat-Diet-Induced Hepatic Steatosis Are SIRT1-Dependent: Evidence from Hepatic-Specific SIRT1 Heterozygous Mutant C57BL/6 Mice
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2022-04-29 , DOI: 10.1021/acs.jafc.2c01461
Yan Yin ₁ , Deming Li ₁ , Fang Liu ₁ , Xinjing Wang ₁ , Yuan Cui ₁ , Shilan Li ₁ , Xinli Li _{1,

2}

Affiliation

Apple polyphenol extract (APE) has been reported to possess protective effects against hepatic steatosis. To explore whether APE-induced alleviation of hepatic steatosis is SIRT1-dependent, the present study was carried out using wild-type and hepatic SIRT1 heterozygous mutant (Sirt1^+/–) C57BL/6 mice. On consideration of the sex disparity related to hepatic steatosis morbidity, both male and female mice were included in the study. Six to eight week old mice were fed a high-fat diet (HFD) and randomly assigned to one of the following groups: (1) wild-type mice (wt+HFD), (2) Sirt1^+/– mice (Sirt1^+/–+HFD), and (3) Sirt1^+/– mice with 500 mg/(kg·bw·d) APE intragastric administration (Sirt1^+/–+HAP). HFD-induced weight gain and triglyceride accumulation was more prominent in Sirt1^+/– mice in comparison to wild-type mice. Following APE treatment, these effects were significantly reduced along with the alleviation of hepatic steatosis via upregulated expression of SIRT1 at the protein and mRNA levels in both male and female mice. However, APE differentially regulated the genes related to lipid metabolism (Lkb1, Ampk, Hsl, Srebp-1c, Abcg1, and Cd36) in a sex-specific manner. Moreover, APE treatment altered gut microbiota composition, with an increased relative abundance of Akkermansia and a decreased Firmicutes/Bacterodetes ratio. Thus, our study provided new evidence supporting our hypothesis that APE-induced alleviation of hepatic steatosis is SIRT1-dependent.

中文翻译：

苹果多酚提取物对高脂饮食诱导的肝脏脂肪变性的改善作用依赖于 SIRT1：来自肝脏特异性 SIRT1 杂合突变体 C57BL/6 小鼠的证据

据报道，苹果多酚提取物 (APE) 对肝脏脂肪变性具有保护作用。为了探索 APE 诱导的肝脏脂肪变性缓解是否依赖于 SIRT1，本研究使用野生型和肝脏 SIRT1 杂合突变体 (Sirt1 ^+/– ) C57BL/6 小鼠进行。考虑到与肝脂肪变性发病率相关的性别差异，雄性和雌性小鼠均被纳入研究。6 至 8 周龄小鼠喂食高脂肪饮食 (HFD)，并随机分配到以下组之一：(1) 野生型小鼠 (wt+HFD)，(2) Sirt1 ^+/–小鼠 (Sirt1 ^{+ /–} +HFD)，和 (3) Sirt1 ^+/–小鼠 500 mg/(kg·bw·d) APE 灌胃给药 (Sirt1 ^+/–+HAP）。与野生型小鼠相比，HFD 诱导的体重增加和甘油三酯积累在 Sirt1 ^{+/–小鼠中更为突出。}在 APE 治疗后，通过上调雄性和雌性小鼠的蛋白质和 mRNA 水平上 SIRT1 的表达，这些作用随着肝脏脂肪变性的减轻而显着降低。然而，APE以性别特异性方式差异调节与脂质代谢相关的基因（Lkb1、Ampk、Hsl、Srebp-1c、Abcg1和Cd36 ）。此外，APE 治疗改变了肠道微生物群组成，增加了Akkermansia的相对丰度和降低的厚壁菌门/拟杆菌门比率。因此，我们的研究提供了新的证据支持我们的假设，即 APE 诱导的肝脂肪变性缓解是 SIRT1 依赖性的。

更新日期：2022-04-29

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