Cysteine depletion triggers adipose tissue thermogenesis and weight loss | Hacker News Reader

Cysteine depletion triggers adipose tissue thermogenesis and weight loss

nature.com

97 pointsbookofjoe63 comments

The phrasing of the title and paper steer the interpretation towards reducing cysteine as a method for increasing weight loss, however I think that the much more interesting takeaway is this:

> Notably, restoration of up to 75% cystine levels in the diet of Cth−/− CysF mice that were undergoing weight loss was sufficient to completely rescue the body weight

This might indicate that cysteine depletion could be one mechanism present in some wasting diseases, and that strategic supplementation of cysteine may be beneficial in reducing excessive weight loss in such diseases. I would be quite interested to see future research in this area.

An overview of other studies investigating cysteine and glycine sources and effects (from 2023; video or transcript):

https://nutritionfacts.org/hnta-video/how-to-get-less-cystei...

so... basically limit proteins especially from meat?

"Systemic cysteine depletion in mice causes lethal weight loss"

I didn't read much after that

Maybe you should have.

Cysteine is also an irreplaceable building block of vital proteins required to sustain life. It’s unclear if there is any potential benefit of applying these findings to the problem of human weight loss or fitness.

I agree, for example Pepsin[1] that is the protein inside the stomach that split proteins has Cysteine [2]

> Pepsin forms three between the sulfur atoms of cysteine residues in the peptide chain which hold important roles in the folding of the protein and stabilizing the two domains

[1] https://en.wikipedia.org/wiki/Pepsin

[2] https://biology.kenyon.edu/BMB/jsmol2021/Cat_Marko/index.htm...

Cysteine is not an essential amino acid. Humans can synthesize it from methionine.

These mice were GMO’d to be incapable of synthesising cysteine.

Wikipedia's disclaimers on that: "Cysteine can usually be synthesized by the human body under normal physiological conditions if a sufficient quantity of methionine is available."

I would make a stronger statement and say that this belongs squarely on the effect and not the cause side.

I could be wrong, but I doubt it. Amino acid depletion sounds way more likely to be due to some kind of disruption in homeostasis rather than dietary intake.

Funny because cysteinuria doesn’t do this (pee out cysteine)

Cysteine plays a key role in redox metabolism and removing reactive oxygen species (ROS). During brown fat burning, high flux of electrons increases the NADH/NAD⁺ and FADH₂/FAD ratios — shifting redox state toward a more reduced environment, which is exactly what you would need if deprived of cysteine.

It's difficult to reduce cysteine by diet since it occurs in a wide variety of foods plus reducing it may be harmful as it is used in beneficial ways as well. So more research needed.

This should only act as a clue into driving weight loss. Depleting of cysteine is severe. It would be depriving a team from writing html and discovery the code runs faster… very drastic imposition

(In mice)

This 2012 study in humans says

> Since this was also a noninterventional study, two possibilities for interpretation of the findings were either that a high cysteine somehow promotes obesity or that obesity influences cysteine turnover, thereby raising plasma tCys.

https://onlinelibrary.wiley.com/doi/full/10.1038/oby.2011.93

In genetically modified mice.

(So far)

(also observed to be lethal in cases)

Cysteine protease inhibitors could be used to reduce free cysteine available to cells. Some natural sources of those are papaya, kiwi, pineapple, fig, apples, and rice.

Cysteine proteases are named after their reaction mechanism, which involves a key cysteine residue within the enzyme. It doesn't have anything to do with the amino acids in the cleaved proteins.

Is this the same as homocysteine?

So, does taking NAC make me fat? If I stop taking NAC, will it help me lose weight?

According to the article, you’ll lose so much weight that you need euthanasia if you stop taking NAC - but only if you’re also a mice that also happens to be genetically modified to not produce any Cysteine biologically. Oh, and you shouldn’t eat anything containing cysteine naturally.

Gotcha. So basically I’m going to be fat no matter what, you’re saying.

Another linked article suggests that NAC administration if anything causes weight loss, and has a lot of opposite effects as cysteine. I don't think they're interchangeable.

Interesting. I missed that.

If only there were NAC that doesn't stink opening the bottle.

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