反式脂肪如何加速细胞死亡 How trans fats fastens cell death

News Release 25-Mar-2020

Some trans fats enhance a pathway inside the cell that leads to cell death; drugs targeting this mechanism could help address diseases associated with these fats

Tohoku University

Tohoku University researchers in Japan have uncovered a molecular link between some trans fats and a variety of disorders, including cardiovascular and neurodegenerative diseases. Their findings, published in the journal Scientific Reports, implicate their role in enhancing a mitochondrial signalling pathway that leads to programmed cell death.

“Accumulating evidence has associated the consumption of trans-fatty acids with various diseases, including some lifestyle diseases, atherosclerosis and dementia. But the underlying causes have remained largely unknown,” says Atsushi Matsuzawa of Tohoku University’s Laboratory of Health Chemistry.

Matsuzawa and a team of researchers explored the effects of two trans fats produced during industrial food manufacturing, elaidic and linoelaidic acids, on programmed cell death.

Cells instigate programmed cell death, which is called apoptosis, if their DNA is damaged beyond repair. DNA damage can occur in response to a variety of factors, including reactive oxygen species, ultraviolet irradiation and anti-cancer drugs. Normally, cells counteract this process by repairing the lesions. But problems in the DNA damage response can lead to diseases also associated with trans fats.

The researchers induced DNA damage in cells using the anti-cancer drug doxorubicin. They found that elaidic and linoelaidic acids enhanced the apoptosis that followed. Other unsaturated fatty acids did not have the same effect.

Specifically, they found the fatty acids affected mitochondria, the energy-generating powerhouses of cells. DNA damage activates a signalling loop inside mitochondria that generates reactive oxygen species, which ultimately promote apoptosis. The industrial trans fats enhanced mitochondria’s production of reactive oxygen species through this signalling loop, and thus increased apoptosis.

Apoptosis is thought to lead to the development and progression of disorders associated with industrial trans fats, such as the build-up of plaque inside arteries, called atherosclerosis.

“Our research revealed a novel toxic function and mechanism of action of trans-fatty acids, which can account for pathological mechanisms, including atherosclerosis,” says Matsuzawa. “This significant finding will provide a molecular basis to understand how trans-fatty acids cause disease.”

The researchers theorize that targeting this molecular mechanism with drugs might have a therapeutic effect on a diverse range of trans-fat-associated diseases. The team plans to further investigate this link and the extent to which this mechanism contributes to these diseases. They also aim to determine the differences in toxicity between different trans fats.

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新闻稿2020年3月25日
反式脂肪如何帮助细胞死亡

一些反式脂肪会增强细胞内导致细胞死亡的途径；针对这种机制的药物可能有助于解决与这些脂肪有关的疾病

东北大学

图像：吃含有反式脂肪的食物会导致心血管疾病和神经退行性疾病的发病率升高。现在，科学家对反式脂肪产生负面影响的过程有了更好的了解。…查看更多

学分：东北大学

日本东北大学的研究人员发现了一些反式脂肪与包括心血管疾病和神经退行性疾病在内的多种疾病之间的分子联系。他们的发现发表在《科学报告》杂志上，暗示了他们在增强导致程序性细胞死亡的线粒体信号传导途径中的作用。

东北大学健康化学实验室的松泽淳说：“越来越多的证据表明，反式脂肪酸的摄入与多种疾病有关，包括一些生活方式疾病，动脉粥样硬化和痴呆。但是，其根本原因仍然未知。”

Matsuzawa和一组研究人员探讨了工业食品生产过程中产生的两种反式脂肪，亚麻酸和亚油酸，对程序性细胞死亡的影响。

如果细胞的DNA受损而无法修复，则会引发程序性细胞死亡，这称为细胞凋亡。 DNA损伤可能是由于多种因素引起的，包括活性氧，紫外线照射和抗癌药。通常，细胞通过修复病变来抵消这一过程。但是，DNA损伤反应中的问题可能导致与反式脂肪有关的疾病。

研究人员使用抗癌药阿霉素诱导了细胞DNA的损伤。他们发现，亚麻酸和亚麻油酸增强了随后的细胞凋亡。其他不饱和脂肪酸没有相同的作用。

具体来说，他们发现脂肪酸影响线粒体，线粒体是细胞产生能量的动力。 DNA损伤激活了线粒体内的信号转导环，从而产生活性氧，最终促进细胞凋亡。工业反式脂肪通过该信号回路增强了线粒体活性氧的产生，从而增加了细胞凋亡。

人们认为细胞凋亡会导致与工业反式脂肪相关的疾病的发展和进展，例如动脉内斑块的积聚，称为动脉粥样硬化。

松泽说：“我们的研究表明反式脂肪酸具有新颖的毒性功能和作用机制，这可以解释包括动脉粥样硬化在内的病理机制。” “这一重要发现将为理解反式脂肪酸如何引起疾病提供分子基础。”

研究人员认为，用药物靶向这种分子机制可能对多种与反式脂肪相关的疾病具有治疗作用。研究小组计划进一步研究这种联系，以及这种机制导致这些疾病的程度。他们还旨在确定不同反式脂肪之间毒性的差异。

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