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Comment by manmal | Hacker News Reader

I‘m confused, studies like this one [1] associate decreased fatty acid oxidation in the heart with heart enlargement and subsequent heart failure. Does this concern different cell types?

1: https://pubmed.ncbi.nlm.nih.gov/35365608/

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It probably matters immensely which specific molecule is blocked and if you block one too early in some process then critical intermediates can’t be made. Sort of like deleting some code, it matters what’s downstream, so maybe earlier parts of this process are bad to block, but if you have a heart attack, then blocking later parts of the same process could trick your heart cells back into regenerating instead of being stable.

Also worth noting, this could be an example of hormesis. A metabolic approach to de-differentiate heart cells into a more primitive form by disrupting the way they process fats could be considered a toxic insult which triggers some defense (stemness) which is the proximate cause / helpful thing (not the toxic insult)

The study you linked shows that fatty acid oxidation accelerates cardiac hypertrophy.

The study linked above shows that fatty acid oxidation results in apparent hyperplastic and hypertrophic growth of the myocardium.

There are some significant differences between the observations in both studies, though, so they're not directly comparable. I wouldn't say they contradict each other though.

The two studies also reduced fatty acid oxidation very differently: One via microbiome manipulation and the other via genetic manipulation. Both routes will have side effects well beyond this singular measure, so they can't be compared directly.

Regardless, neither study is meant to indicate a viable medical procedure. The researchers are teasing out mechanisms that might be harnessed in the future to do something more useful.

Does that contradict what is being said here, though? The straightforward reconciliation of the two: Some inhibition leads to regeneration; extended inhibition leads to runaway growth leading to abnormally enlarged cardiomusculature and health complications?

(I haven’t yet clicked your link, though!)

Almost for any study that says X, you will find another one that says exactly the inverse.

Don’t know about the exact inverse. But disease X could be improved while disease Y risk rises. It’s curious that both studies are about cardiac health. Maybe there’s different types of FAO, or FAO is desirable in some cell types but not in others.

If you have fifty different groups studying roughly the same thing and publishing any interesting-looking results with p<.05, you're probably going to have some spurious results on the topic. If you have 500 groups, you're going to have a lot of spurious and probably some outright contradictory results published.

In many cases, with large enough numbers, the spurious results will outnumber the real ones, especially so since true-null-hypothesis results are often unpublished.

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