How saturated fatty acids damage cells
Observations of Saturated and Unsaturated Fatty Acid Behavior Could Impact Public Health
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。
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。
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
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