哥伦比亚大学：观察到饱和脂肪和不饱和脂肪如何影响细胞膜的流动性

How saturated fatty acids damage cells

Observations of Saturated and Unsaturated Fatty Acid Behavior Could Impact Public Health

 

　

导读：

1. 细胞膜是氧气和各种营养素进入细胞，以及排泄细胞代谢废物的门户；

2. 科学家首次直接观察到活细胞内脂肪酸的分布和动态；

3. 饱和脂肪使细胞膜变得“冰冻”-硬化，失去流动性；而不饱和脂肪则可以”融化“饱和脂肪的冷冻膜岛，恢复细胞膜的流动性；

4. 哥伦比亚大学的这个发现证实了德国科学家巴德维博士在1950年代提出的观点-反式脂肪和饱和脂肪令细胞窒息，并且是导致癌症和许多慢性疾病的重要原因；

　

　

　

在我们日益健康的社会中，每隔几年就会出现一种新的时尚饮食。 Atkins，Zone，Ketogenic，Vegetarian，Vegan，South Beach，Raw  - 有很多选择和科学证据支持每一个，很难知道什么是健康的，什么不是。然而，有一条信息始终存在：饱和脂肪是有害的。

 

哥伦比亚大学新的研究揭示了原因。

 

虽然医生，营养学家和研究人员长期以来都知道饱和脂肪是造成美国某些主要死亡原因的原因，但他们无法确定过量饱和脂肪的方式或原因，例如从猪油中释放出来的脂肪。对细胞有毒并引起各种与脂质有关的疾病，而不饱和脂肪，如鱼和橄榄油，可以起到保护作用。

 

为了找到答案，研究人员开发了一种新的显微镜技术，可以在脂肪酸被活细胞吸收后直接追踪脂肪酸。该技术涉及用同位素，氘取代脂肪酸上的氢原子，而不像传统策略那样改变它们的物理化学性质和行为。通过切换，所有由脂肪酸制成的分子都可以通过称为受激拉曼散射（SRS）显微镜的先进成像技术在活细胞内观察到。

 

 

研究人员发现使用这种技术可以对肥胖，糖尿病和心血管疾病的理解和治疗产生重大影响。

 

该研究小组于12月1日在线发表在美国国家科学院院刊（PNAS）上报道，用饱和脂肪酸构建细胞膜的细胞过程会产生硬化膜片，其中分子被“冻结”。在健康的条件下，这种膜应该是柔韧的，分子是流动的。

 

研究人员解释说，饱和脂肪酸的僵硬，直的长链使脂质分子僵硬，并使它们与细胞膜的其他部分分离。在他们的显微镜下，研究小组观察到这些脂质分子会聚集在紧密堆积的“岛屿”或簇中，这些岛屿不会移动太多 - 他们称之为“固体状态”。随着更多的饱和脂肪酸进入细胞，这些岛屿的大小增加，导致膜的无弹性增加，并逐渐损坏整个细胞。

 

“长期以来，我们相信所有的细胞膜都是液体状的，允许嵌入的蛋白质改变它们的形状并进行反应，”首席研究员魏敏，化学教授说。 “之前在活哺乳动物细胞中几乎观察不到固体样膜。我们看到的是完全不同和令人惊讶的。“

 

另一方面，由不饱和脂肪酸制成的脂质分子在其链中产生扭结，Min说，这使得这些脂质分子不可能像饱和脂肪分子那样彼此紧密排列。它们继续自由移动而不是形成固定的簇。在它们的运动中，这些分子可以在紧密堆积的饱和脂肪酸链之间挤压和滑动。

 

“我们发现添加不饱和脂肪酸可以”融化“被饱和脂肪酸冷冻的膜岛，”第一作者闵晖晖说，他是闵实验室的研究生。她说，这种新机制可以部分解释不饱和脂肪酸的有益作用，以及鱼油中的不饱和脂肪如何在一些脂质紊乱中起到保护作用。

 

Shen补充说，这项研究首次表明研究人员能够直观地观察活细胞内脂肪酸的分布和动态，并揭示了细胞膜内饱和脂质积聚的先前未知的毒性物理状态。

 

“一旦他们进入细胞，饱和脂肪酸的行为就会导致严重的，往往是致命的疾病，”敏说。 “可视化脂肪酸如何促成脂质代谢疾病，为我们提供了开始寻找有效治疗方法所需的直接物理信息。或许，例如，我们可以找到阻止有毒脂质积累的方法。我们很兴奋。这一发现有可能真正影响公众健康，尤其是与脂质相关的疾病。“

　

Columbia University: Observations of Saturated and Unsaturated Fatty Acid Behavior Could Impact Public Health

　

In our increasingly health-conscious society, a new fad diet seems to pop up every few years. Atkins, Zone, Ketogenic, Vegetarian, Vegan, South Beach, Raw – with so many choices and scientific evidence to back each, it’s hard to know what’s healthy and what’s not. One message, however, has remained throughout: saturated fats are bad.

 

A new Columbia University study reveals why.

 

While doctors, nutritionists and researchers have known for a long time that saturated fats contribute to some of the leading causes of death in the United States, they haven’t been able to determine how or why excess saturated fats, such as those released from lard, are toxic to cells and cause a wide variety of lipid-related diseases, while unsaturated fats, such as those from fish and olive oil, can be protective.

 

To find answers, researchers developed a new microscopy technique that allows for the direct tracking of fatty acids after they’ve been absorbed into living cells. The technique involves replacing hydrogen atoms on fatty acids with their isotope, deuterium, without changing their physicochemical properties and behavior like traditional strategies do. By making the switch, all molecules made from fatty acids can be observed inside living cells by an advanced imaging technique called stimulated Raman scattering (SRS) microscopy.

 

What the researchers found using this technique could have significant impact on both the understanding and treatment of obesity, diabetes and cardiovascular disease.

 

Published online December 1st in Proceedings of the National Academy of Sciences (PNAS), the team reports that the cellular process of building the cell membrane from saturated fatty acids results in patches of hardened membrane in which molecules are “frozen.” Under healthy conditions, this membrane should be flexible and the molecules fluidic.

 

The researchers explained that the stiff, straight, long chains of saturated fatty acids rigidify the lipid molecules and cause them to separate from the rest of the cell’s membrane. Under their microscope, the team observed that those lipid molecules then accumulate in tightly-packed “islands,” or clusters, that don’t move much – a state they call “solid-like.” As more saturated fatty acids enter the cell, those islands grow in size, creating increasing inelasticity of the membrane and gradually damaging the entire cell.

 

“For a long time, we believed that all cell membrane is liquid-like, allowing embedded proteins to change their shape and perform reactions,” said Principal Investigator Wei Min, a professor of chemistry. “Solid-like membrane was hardly observed in living mammalian cells before. What we saw was quite different and surprising.”

 

Lipid molecules made from unsaturated fatty acids on the other hand bear a kink in their chains, Min said, which makes it impossible for these lipid molecules to align closely with each other as saturated ones do. They continue to move around freely rather than forming stationary clusters. In their movement, these molecules can jostle and slide in between the tightly-packed saturated fatty acid chains.

 

“We found that adding unsaturated fatty acids could ‘melt’ the membrane islands frozen by saturated fatty acids,” said First Author Yihui Shen, a graduate student in Min’s lab. This new mechanism, she said, can partly explain the beneficial effect of unsaturated fatty acids and how unsaturated fats like those from fish oil can be protective in some lipid disorders.

 

The study represents the first time researchers were able to visualize the distribution and dynamics of fatty acids in such detail inside living cells, Shen added, and it revealed a previously unknown toxic physical state of the saturated lipid accumulation inside cellular membranes.

 

“The behavior of saturated fatty acids once they’ve entered cells contributes to major and often deadly diseases,” Min said. “Visualizing how fatty acids are contributing to lipid metabolic disease gives us the direct physical information we need to begin looking for effective ways to treat them. Perhaps, for example, we can find a way to block the toxic lipid accumulation. We’re excited. This finding has the potential to really impact public health, especially for lipid related diseases."

 

-By Jessica Guenzel

 

Journal Reference:

 

Yihui Shen, Zhilun Zhao, Luyuan Zhang, Lingyan Shi, Sanjid Shahriar, Robin B. Chan, Gilbert Di Paolo, Wei Min. Metabolic activity induces membrane phase separation in endoplasmic reticulum. Proceedings of the National Academy of Sciences, 2017; 201712555 DOI: 10.1073/pnas.1712555114

 

New Imaging Study Reveals How Saturated Fatty Acids Damage Cells | Columbia News  https://news.columbia.edu/content/1792

https://www.sciencedaily.com/releases/2017/12/171201181545.htm