Transgenic overexpression of CTRP3 prevents alcohol-induced hepatic triglyceride accumulation.
Transgenic overexpression of CTRP3 prevents alcohol-induced hepatic triglyceride accumulation.
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CTRP3 的转基因过度表达可防止酒精诱导的肝脏甘油三酯积累。
DOI：
10.1152/ajpendo.00050.2018
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Peterson,JonathanM
中科院分区：
文献类型：
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作者：
Trogen,Greta;Bacon,Joshua;Li,Ying;Wright,GaryL;Degroat,Ashley;Hagood,KendraL;Warren,Zachary;Forsman,Allan;Kilaru,Aruna;Clark,WAndrew;Peterson,JonathanM
这项研究测试了一种新型脂肪组织衍生细胞因子 C1q TNF 相关蛋白 3 (CTRP3) 预防酒精引起的肝脏脂质积累或酒精性脂肪肝 (ALD) 的能力。前期工作已证明CTRP3可有效预防高脂饮食诱发的脂肪肝；然而，CTRP3 抑制 ALD 的潜力尚未被探索。为了测试 CTRP3 的潜在保护作用，将过表达 CTRP3 (Tg) 的转基因小鼠或野生型同窝小鼠 (WT) 置于两种不同的 ALD 模型中的一种。在第一个模型（称为 NIAAA 模型）中，小鼠被喂食对照或含酒精液体饮食（5% vol/vol）10 天，然后单次灌胃乙醇（5 g/kg）。在第二个模型（慢性模型）中，小鼠被喂食对照或含酒精饮食 6 周，但不强饲。这项研究发现，CTRP3 将慢性饮酒模型中的甘油三酯积累减少了约 50%，而在 NIAAA 模型中没有观察到减少。对来自 WT 和 Tg 小鼠的分离原代肝细胞的进一步分析表明，CTRP3 在存在脂肪酸的情况下增加了耗氧量，表明 CTRP3 增加了肝脂肪酸的利用率。总之，这项研究表明，CTRP3 会减弱肝脏甘油三酯的积累，以应对长期慢性饮酒，但不会影响短期饮酒。
This study tested the ability of a novel adipose tissue derived cytokine, C1q TNF-related protein-3 (CTRP3), to prevent alcohol-induced hepatic lipid accumulation, or alcoholic fatty liver disease (ALD). Previous work has demonstrated that CTRP3 is effective at preventing high-fat diet-induced fatty liver; however, the potential of CTRP3 to inhibit ALD has not been explored. To test the potential protective effects of CTRP3, transgenic mice overexpressing CTRP3 (Tg) or wild-type littermates (WT) were subjected to one of two different models of ALD. In the first model, known as the NIAAA model, mice were fed control or alcohol-containing liquid diets (5% vol/vol) for 10 days followed by a single gavage of ethanol (5 g/kg). In the second model, the chronic model, mice were fed control or alcohol-containing diets for 6 wk with no gavage. This study found that CTRP3 reduced triglyceride accumulation in the chronic model of alcohol consumption by ~50%, whereas no reduction was observed in the NIAAA model. Further analysis of isolated primary hepatocytes from WT and Tg mice demonstrated that CTRP3 increased oxygen consumption in the presence of fatty acids, indicating that CTRP3 increases hepatic fatty acid utilization. In conclusion, this study indicates that CTRP3 attenuates hepatic triglyceride accumulation in response to long-term chronic, but not short-term, alcohol consumption.