Dynamic Alterations to Hepatic MicroRNA-29a in Response to Long-Term High-Fat Diet and EtOH Feeding.
Dynamic Alterations to Hepatic MicroRNA-29a in Response to Long-Term High-Fat Diet and EtOH Feeding.
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DOI：
10.3390/ijms241914564
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发表时间：
2023-09-26
影响因子：
5.6
通讯作者：
Chalasani N
中科院分区：
文献类型：
--
作者：
Liang T;Kota J;Williams KE;Saxena R;Gawrieh S;Zhong X;Zimmers TA;Chalasani N
MicroRNA-29a (miR-29a) 是一种特征明确的纤维炎症分子，其异常表达与多种肝脏病理状况有关。高脂肪饮食 (HFD) 与不同水平的 EtOH 消耗相结合对 miR-29a 表达和肝脏病理学的长期影响尚不清楚。将8周龄的小鼠分为五组（热量匹配饮食加水（CMD）作为对照组，HFD加水（HFD）作为肝病组，HFD加2％EtOH（HFD + 2％E），HFD + 10％E和HFD + 20％E作为干预组）并喂养4、13、26或39周。在每个时间点，对肝脏重量/体重 (BW) 比率、AST/ALT 比率以及肝脏组织学评估进行分析，其中包括炎症、估计脂肪沉积、脂质面积和纤维化。测量肝脏 miR-29a 并确定与表型性状的相关性。 4 周喂养对所有收集的表型性状或 miR-29a 表达没有产生组间差异，而 13 周后观察到 EtOH 浓度特异性诱导 miR-29a 的显着效果。大多数收集到的性状在第 26 周时出现了明显的转折点，随着肝损伤的加重，miR-29a 显着下调。总体而言，miR-29a 上调与较低的肝脏/体重比、脂肪沉积、炎症和纤维化相关，表明 miR-29a 对肝脏疾病进展具有保护作用。 HFD 加上浓度不断增加的乙醇会对肝脏产生渐进的不利影响，但没有证据表明低剂量乙醇消耗有有益作用。此外，miR-29a 上调与较轻的肝损伤相关。
MicroRNA-29a (miR-29a) is a well characterized fibro-inflammatory molecule and its aberrant expression is linked to a variety of pathological liver conditions. The long-term effects of a high-fat diet (HFD) in combination with different levels of EtOH consumption on miR-29a expression and liver pathobiology are unknown. Mice at 8 weeks of age were divided into five groups (calorie-matched diet plus water (CMD) as a control group, HFD plus water (HFD) as a liver disease group, HFD plus 2% EtOH (HFD + 2% E), HFD + 10% E, and HFD + 20% E as intervention groups) and fed for 4, 13, 26, or 39 weeks. At each time point, analyses were performed for liver weight/body weight (BW) ratio, AST/ALT ratio, as well as liver histology assessments, which included inflammation, estimated fat deposition, lipid area, and fibrosis. Hepatic miR-29a was measured and correlations with phenotypic traits were determined. Four-week feeding produced no differences between the groups on all collected phenotypic traits or miR-29a expression, while significant effects were observed after 13 weeks, with EtOH concentration-specific induction of miR-29a. A turning point for most of the collected traits was apparent at 26 weeks, and miR-29a was significantly down-regulated with increasing liver injury. Overall, miR-29a up-regulation was associated with a lower liver/BW ratio, fat deposition, inflammation, and fibrosis, suggesting a protective role of miR-29a against liver disease progression. A HFD plus increasing concentrations of EtOH produces progressive adverse effects on the liver, with no evidence of beneficial effects of low-dose EtOH consumption. Moreover, miR-29a up-regulation is associated with less severe liver injury.
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影响因子：
29.4
作者：
Chen P;Torralba M;Tan J;Embree M;Zengler K;Stärkel P;van Pijkeren JP;DePew J;Loomba R;Ho SB;Bajaj JS;Mutlu EA;Keshavarzian A;Tsukamoto H;Nelson KE;Fouts DE;Schnabl B
通讯作者：
Schnabl B
影响因子：
5.6
作者：
Huang YH;Yang YL;Wang FS
通讯作者：
Wang FS
DOI：
10.1165/rcmb.2010-0323oc
发表时间：
2011-08-01
影响因子：
6.4
作者：
Cushing, Leah;Kuang, Ping Ping;Lue, Jining
通讯作者：
Lue, Jining
影响因子：
6.1
作者：
Echeverria, Francisca;Valenzuela, Rodrigo;Videla, Luis A.
通讯作者：
Videla, Luis A.
影响因子：
21.1
作者：
Dopico AM;Lovinger DM
通讯作者：
Lovinger DM