How Saturated Fatty Acids Damage Cells

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Magda
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How Saturated Fatty Acids Damage Cells

Post by Magda »

New technology is amazing!
Below is a an articular about new findings on saturated fats from Columbia University.
Researches have developed a new microscopy technique that allows for direct tracking of fatty acids after they have 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.


Here is what the reserches have found:

https://www.sciencedaily.com/releases/2 ... 181545.htm

"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, Columbia 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."

Story Source:

Materials provided by Columbia University

. Note: Content may be edited for style and length.
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
Last edited by Magda on Wed Dec 13, 2017 2:46 pm, edited 1 time in total.
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Re: How Saturated Fatty Acids Damage Cells

Post by MarcR »

This is a fascinating analysis from Science Daily as it has almost nothing to do with the actual paper it purports to summarize. I would encourage anyone concerned about dietary saturated fat because of this study summary to read the paper itself - when I did so, I concluded that Science Daily is way off in the weeds here. The paper is a highly technical description of a promising new technique for observation of cellular lipid dynamics. The authors present no evidence, let alone conclusions, regarding cellular damage due to saturated fatty acids. Needless to say, the paper also concerns itself not at all with the nutritional effects of saturated fat consumption.

For a detailed discussion of evidence regarding the role of dietary saturated fat in human health, I would encourage newcomers to read this thread.
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Re: How Saturated Fatty Acids Damage Cells

Post by SusanJ »

Medical Xpress printed the same thing, so they are just passing through the press release from Columbia. Shen's thesis evidently looked at saturated fat. Guessing she combined the two for the press release material. https://chem.columbia.edu/events/thesis ... meostasis/
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Re: How Saturated Fatty Acids Damage Cells

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Deuterium can negatively impact mitochondrial functioning. It is commonly used to "tag" things that are the object of study, however it may not be benign and there are treatments to deplete body stores of deuterium to positively impact areas of health such as cancer...
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Re: How Saturated Fatty Acids Damage Cells

Post by Orangeblossom »

Interesting. Yes definitely better to look at the source article.

From the article it seems to be more of a problem with long chain fatty acids such as ones from palm oil and less with shorter chain fatty acids.

"We went on to test a set of deuterated SFAs including lauric acid (C12:0), myristic acid (C14:0), palmitic acid (C16:0), and stearic acid (C18:0). Their metabolites show elevating Tm values due to increasing fatty acyl chain lengths (Table S1). In agree- ment with our hypothesis, they exhibited increasing capability to drive large-scale phase separation at the same concentration (Fig. 6B): C12:0 does not form visible membrane domains but numerous LDs even after prolonged treatment; C14:0 only forms domains with limited size (∼1 μm); C18:0 forms large-scale membrane structures even faster than C16:0 does."

And about the interaction between the fats:

"Similar to oleate, docosahexaenoic acid (DHA) (22:6), a polyunsaturated fatty acid, was also able to reduce the area of palmitate-derived solid membrane domains" (Oleate seems to come from oleic acid)

I do eat sat fats but also plenty of oleic acid from avocados, DHA and EVOO so guess that is OK. I remember some advice about eating a variety of types of fat from one of Hyman's books - he recommended omega 3's alongside other sat fats I remember.

It says palmitic acid is the most common fatty acid around but I'm not sure about that in the UK anyway. I notice things like nut butters say 'no palm oil' and I don't see it in many foods. :?
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Re: How Saturated Fatty Acids Damage Cells

Post by Orangeblossom »

I noticed in reading about sat fats and APOE4, it is worrying that some papers focus on things like spreads to deduce sat fats are not good for us. Like this one which I guess many have seen before about how lifestyle affects us in different ways.

Anyone who has read about fats would know that 'spreads' can be bad for us. but it is important not just to think from that all natural unprocessed sources are, too.

Apolipoprotein E ε4 magnifies lifestyle risks for dementia: a population-based study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828889/

"the associations between dementia and moderate SFA intake, frequent alcohol drinking and physical inactivity were more pronounced among the apoE ε4 carriers than non-carriers. Furthermore, there was also a tendency towards increased odds of dementia for high-dietary SFA intake, infrequent alcohol drinking and smoking among the apoE ε4 carriers."

but then, in the details..

"Dietary fat intake was determined as daily fat intake from spreads, and the amount of polyunsaturated (PUFA) and saturated (SFA) fatty acids were calculated from these data." :roll: Most spreads contain things like palm oil...hydrogenated perhaps...probably with things like trans fats as well.

Also, it concludes "Our findings suggest that physical activity, sufficient intake of PUFA and avoiding excess SFA intake, alcohol drinking and smoking may decrease the risk or postpone the onset of dementia especially among the apoE ε4 carriers." However in the table of results, high PUFA seems to increase the risk in E4s in a similar way to the 'sat fats' :?

It's all a bit confusing and not sure why they don't also include trans fats. (as looking at spreads).
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Re: How Saturated Fatty Acids Damage Cells

Post by Indy3/4 »

Mark's Daily Apple posted two articles regarding the recent Shen et al. saturated fat study. Although neither article addresses Apoe4 carriers, Mark's insight to this study is of interest.

Article #1

Article #2
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Re: How Saturated Fatty Acids Damage Cells

Post by Orangeblossom »

Good articles. I like avocado oil, you can get it with lemon in and it tastes really nice. as an aside.
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Re: How Saturated Fatty Acids Damage Cells

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This is an exvivo study. All it really does is confirm older research on the metabolic nature of saturated fat and unsaturated fat on membrane fluidity. Revici's three-decades of research on this was published in 1961, which was developed from studies of living animals, including human cancer patients. This is important to consider because real, biological membranes (not fatty-acid rafts on a SERS surface) balance the membrane permeability by the relative influence of cholesterol between the bio-membrane bi-layers (!), not just the balance between saturated fatty acids and unsaturated fatty acids. All this research did was study the fluidity of fatty acid rafts, which when saturated pack nicely into highly structured "stacks," like a mostly filled box of toothpicks, or like tree logs stacked to dry before being cut into lumber. As I said, this is old information and of minimal insight. The presence of unsaturated carbon-carbon bonds changes the parallel-stacking dynamic. It changes it slightly when the unsaturated bonds are trans (still in a straight line, but with an pi-electron "bulge") and severely when cis (kinked, and no longer straight). Temperate-climate food oils are hugely cis. The "kinks" from the presence of unsaturated and polyunsaturated fats disrupt the parallel stacking of saturated fatty acid strands and leave tiny voids scattered through the lipid layer, through which small molecules can more easily slide. This ease of sliding is described as permeability, but which can be thought of as "breathability." The problem with talking about saturated fat as frozen is that it is not. At body temperature, these molecules are vibrating with tremendous energies. They might be analogous to plastic straws packed into a paint can being vibrated by a turned-on paint-mixer. Sure, they are more stable in their packing than straws mixed with ping-pong balls on the same paint mixer, but they are not frozen in any real-life meaningful way. In biological membranes (two layers instead of one), there is a cholesterol layer between the two membranes which modulates the permeability of the lipid bilayer. The cholesterol molecules are flat, unlike the linear or stringy fatty acids. This flatness characteristic is distinctly different from stringiness, and instead of stacking like toothpicks, they stack like spread-out playing cards dumped on a table top. And because the cholesterol stacking is sandwiched between two fatty-acid membranes, the cholesterol playing cards are oriented perpendicularly to the fatty-acid toothpicks. This blocks the flow of small molecules through the membrane. So it is not just saturated fatty acids which play the role of down-regulators of membrane permeability and polyunsaturated fatty acids which up-regulate membrane permeability, as suggested by this public-service announcement (a politically motivated bit of science designed to reach a pre-conceived conclusion for educating the public), it is more like saturated fat is permeability neutral and polyunsaturated fats as the up-regulator and cholesterol as down-regulator. Since fatty acid rafts do not contain cholesterol, this study is of limited use, only confirming what science had discovered a hundred years ago, but doing so in a machine-that-goes-beep-beep kind of way (Raman spectroscopy) . So please feel free to chuckle like you would when watching a Monty Python spoof. But this study is hardly worth the publicity and promotion it has received--except for its support of the dead-but-not-dead theory of cholesterol and saturated fat as the bane of human health and welfare. Caveat emptor. Thank you Carol for sending me a link.
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