Are Unsaturated Fatty Acids Worth Considering?

One of the 'advantages' (how strange to use that word) of EHE resulting from a single genetic mutation is the possibility that there might be single actionable targets. Somewhere down the road it might be possible to use gene editing to specifically remove or reduce the expression of the fusion gene responsible for EHE. It's likely a long time until gene editing techniques like CRISPR cas 9  are sufficiently safe and effective for use in humans. Meantime, we can think of interfering with signaling pathways upstream of YAP/TAZ but there's a concern that 1) constitutive activation of the fusion means it's always turned on and therefore not susceptible to upstream manipulation and 2) inhibiting intermediate signals could further activate other upstream paths that are no longer attenuated by feedback inhibition. So, lets look to third way: 

Might it be possible to find a way to accelerate degradation of YAP/TAZ in a way that effectively deactivates them? Well, a recent paper from China suggests that omega-3 polyunsaturated fatty acids (w-3PUFA)might do just that. Kun Zhang et al report in a paper published in Scientific Reports last May that w-3PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce fibrosis in a mouse model of liver damage and fibrosis caused by carbon tetrachloride. This phenomenon is similar to cirrhosis caused by alcohol and is mediated by activation of YAP/TAZ. They further show that EPA and DHA reduce cellular content of YAP/TAZ and that this results from the increased degradation of these proteins. Note that DHA and EPA are common constituents of fish oil. So, could consuming fish oil accelerate degradation of YAP/TAZ in a state like EHE where these proteins are otherwise always active?  I'm not ready to start recommending fish oil all around; after all, we still don't know what this would do to those upstream signals. BUT, it's certainly something worth testing when we have that mouse model of EHE. Or possibly for someone with aggressive EHE when other treatments don't appear to have any benefit.  

 

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