Liver Protein Expression in NASH Mice on a High-Fat Diet: Response to Multi-Mineral Intervention.
Liver Protein Expression in NASH Mice on a High-Fat Diet: Response to Multi-Mineral Intervention.
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纳什小鼠在高脂饮食中的肝蛋白表达：对多矿物干预的反应。
DOI：
10.3389/fnut.2022.859292
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发表时间：
2022
影响因子：
5
通讯作者：
Aslam, Muhammad N.
中科院分区：
文献类型：
--
作者：
Varani, James;McClintock, Shannon D.;Knibbs, Randall N.;Harber, Isabelle;Zeidan, Dania;Jawad-Makki, Mohamed Ali H.;Aslam, Muhammad N.
雄性MS-NASH小鼠维持高脂肪饮食16周，有和没有红藻衍生的矿物质。奥贝胆酸（OCA）在相同的菌株和饲料中用作对照。使用维持在标准（低脂肪）啮齿动物食物饮食上的C57 BL/6小鼠作为对照。在研究的活体部分结束时，评估了体重、肝脏重量、肝酶水平和肝脏组织学。对从个体肝脏获得的样品进行串联质量标签标记/质谱分析，以测定蛋白质谱。与维持低脂饮食的小鼠相比，所有高脂肪喂养的小鼠的全身和肝脏重量增加，肝酶（转氨酶）水平增加，广泛脂肪变性/气球样肝细胞变性。还存在肝脏炎症和胶原沉积的组织学证据，但变化程度较低。在补充矿物质的情况下，观察到气球样变性和胶原蛋白沉积适度减少。单独高脂饮食的对照小鼠表现出与脂肪和碳水化合物代谢失调、脂毒性和氧化应激相关的多种蛋白质变化。胆固醇代谢和胆汁酸形成对饮食特别敏感。在接受多矿物质补充沿着高脂饮食的小鼠中，肝毒性降低，这通过几种细胞色素P450酶和其他氧化剂生成部分的水平降低来证明。此外，在补充矿物质的小鼠中也检测到几种角蛋白的表达升高。补充矿物质时观察到的蛋白质变化在OCA中未观察到。我们以前的研究表明，维持高脂肪饮食长达18个月的小鼠会出现终末期肝损伤，包括肝细胞癌。补充矿物质的小鼠基本上可以防止肿瘤形成和其他高脂肪喂养的终末状态后果。本研究确定了高脂饮食喂养小鼠肝脏中发生的早期（16周）蛋白质变化，以及矿物质补充剂如何影响这些蛋白质的表达。这些发现有助于阐明导致终末期肝损伤的早期蛋白质变化以及膳食矿物质可能减轻这种损伤的潜在机制。
Male MS-NASH mice were maintained on a high-fat diet for 16 weeks with and without red algae-derived minerals. Obeticholic acid (OCA) was used as a comparator in the same strain and diet. C57BL/6 mice maintained on a standard (low-fat) rodent chow diet were used as a control. At the end of the in-life portion of the study, body weight, liver weight, liver enzyme levels and liver histology were assessed. Samples obtained from individual livers were subjected to Tandem Mass Tag labeling / mass spectroscopy for protein profile determination. As compared to mice maintained on the low-fat diet, all high-fat-fed mice had increased whole-body and liver weight, increased liver enzyme (aminotransferases) levels and widespread steatosis / ballooning hepatocyte degeneration. Histological evidence for liver inflammation and collagen deposition was also present, but changes were to a lesser extent. A moderate reduction in ballooning degeneration and collagen deposition was observed with mineral supplementation. Control mice on the high-fat diet alone demonstrated multiple protein changes associated with dysregulated fat and carbohydrate metabolism, lipotoxicity and oxidative stress. Cholesterol metabolism and bile acid formation were especially sensitive to diet. In mice receiving multi-mineral supplementation along with the high-fat diet, there was reduced liver toxicity as evidenced by a decrease in levels of several cytochrome P450 enzymes and other oxidant-generating moieties. Additionally, elevated expression of several keratins was also detected in mineral-supplemented mice. The protein changes observed with mineral supplementation were not seen with OCA. Our previous studies have shown that mice maintained on a high-fat diet for up to 18 months develop end-stage liver injury including hepatocellular carcinoma. Mineral-supplemented mice were substantially protected against tumor formation and other end-state consequences of high-fat feeding. The present study identifies early (16-week) protein changes occurring in the livers of the high-fat diet-fed mice, and how the expression of these proteins is influenced by mineral supplementation. These findings help elucidate early protein changes that contribute to end-stage liver injury and potential mechanisms by which dietary minerals may mitigate such damage.
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影响因子：
29.4
作者：
Cotter, Thomas G.;Rinella, Mary
通讯作者：
Rinella, Mary
影响因子：
4.8
作者：
Canaff, L;Petit, JL;Hendy, GN
通讯作者：
Hendy, GN
影响因子：
3
作者：
Pais, Pilar;D'Amato, Massimo
通讯作者：
D'Amato, Massimo
DOI：
10.1016/s2542-5196(21)00285-0
发表时间：
2022-01
期刊：
The Lancet. Planetary health
影响因子：
--
作者：
Bai Y;Herforth A;Masters WA
通讯作者：
Masters WA
影响因子：
6.1
作者：
Carrillo-Lopez, Natalia;Luis Fernandez-Martin, Jose;Benito Cannata-Andia, Jorge
通讯作者：
Benito Cannata-Andia, Jorge