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New imaging study reveals how saturated fatty acids damage cells

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 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.”

Yihui Shen et al, Metabolic activity induces membrane phase separation in endoplasmic reticulum, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1712555114

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