<br>反式脂肪酸的作用机制。,Advances in Nutrition

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反式脂肪酸的作用机制。
Advances in Nutrition ( IF 8.0 ) Pub Date : 2020-05-01 , DOI: 10.1093/advances/nmz125
Antwi-Boasiako Oteng ₁ , Sander Kersten ₁

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人体研究已确定工业反式脂肪酸的摄入与心血管疾病的发展之间存在正相关关系，导致一些国家颁布了限制食品中工业反式脂肪酸的存在的法律。然而，反式脂肪酸不能从人类饮食中完全消除，因为它们也天然存在于反刍动物的肉类和乳制品中。此外，尚未在所有国家实行工业反式脂肪酸禁令。迄今为止，反对反式脂肪酸的流行病学证据远远掩盖了可能解释反式脂肪酸如何实现其破坏作用的机制见解。本综述通过反式脂肪酸与顺式不饱和脂肪酸和饱和脂肪酸（SFA）的并列作用，重点关注反式脂肪酸有害影响的机制。本综述还仔细探讨了反刍动物反式脂肪酸与工业反式脂肪酸具有不同作用的论点。总体而言，体内和体外研究表明，工业反式脂肪酸会促进炎症和内质网 (ER) 应激，尽管程度低于 SFA，而顺式不饱和脂肪酸则可防止 ER 应激和炎症。此外，与顺式不饱和脂肪酸和 SFA 相比，工业反式脂肪酸会促进肝脏中的脂肪储存，但会损害脂肪组织。在培养的肝细胞和脂肪细胞中，工业反式脂肪酸（而非顺式不饱和脂肪酸或 SFA）通过激活甾醇调节元件结合蛋白 (SREBP) 2 介导的基因调节来刺激胆固醇合成途径。有趣的是，尽管工业反式脂肪酸和反刍动物反式脂肪酸对人血浆脂蛋白表现出相似的作用，但在临床前模型中，只有工业反式脂肪酸会促进炎症、内质网应激和胆固醇合成。总体而言，更清楚地了解反式脂肪酸作用的分子机制可能会为治疗以脂质代谢紊乱为特征的疾病创造新的治疗窗口。

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Mechanisms of Action of trans Fatty Acids.

Human studies have established a positive association between the intake of industrial trans fatty acids and the development of cardiovascular diseases, leading several countries to enact laws that restrict the presence of industrial trans fatty acids in food products. However, trans fatty acids cannot be completely eliminated from the human diet since they are also naturally present in meat and dairy products of ruminant animals. Moreover, bans on industrial trans fatty acids have not yet been instituted in all countries. The epidemiological evidence against trans fatty acids by far overshadows mechanistic insights that may explain how trans fatty acids achieve their damaging effects. This review focuses on the mechanisms that underlie the deleterious effects of trans fatty acids by juxtaposing effects of trans fatty acids against those of cis-unsaturated fatty acids and saturated fatty acids (SFAs). This review also carefully explores the argument that ruminant trans fatty acids have differential effects from industrial trans fatty acids. Overall, in vivo and in vitro studies demonstrate that industrial trans fatty acids promote inflammation and endoplasmic reticulum (ER) stress, although to a lesser degree than SFAs, whereas cis-unsaturated fatty acids are protective against ER stress and inflammation. Additionally, industrial trans fatty acids promote fat storage in the liver at the expense of adipose tissue compared with cis-unsaturated fatty acids and SFAs. In cultured hepatocytes and adipocytes, industrial trans fatty acids, but not cis-unsaturated fatty acids or SFAs, stimulate the cholesterol synthesis pathway by activating sterol regulatory element binding protein (SREBP) 2-mediated gene regulation. Interestingly, although industrial and ruminant trans fatty acids show similar effects on human plasma lipoproteins, in preclinical models, only industrial trans fatty acids promote inflammation, ER stress, and cholesterol synthesis. Overall, clearer insight into the molecular mechanisms of action of trans fatty acids may create new therapeutic windows for the treatment of diseases characterized by disrupted lipid metabolism.

更新日期：2019-11-29

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