Sunday, January 08, 2023

Faking it with selenium

 I've looked at this paper in the past, here and here and it is, to say the least, a little dubious in places

High selenium impairs hepatic insulin sensitivity through opposite regulation of ROS

and I really, really want it to be genuine because it supports this hypothesis

High selenium -> high ROS scavenging -> impaired insulin signalling   -> adipose lipolysis

A follow on from this, also plausible, is that

High adipose lipolysis -> excess FFAs to liver -> hepatic ROS from beta oxidation -> hepatic insulin resistance

which would be normal under high FFA oxidation in hepatocytes. I'm willing to accept that reducing ROS in adipocytes might increase ROS in hepatocytes, at a push. But...

These are images taken of hepatocytes from recently euthanased rats fed supplementary selenium for six weeks. This is section A from Figure 3 as a simple copy paste:



















What we are comparing is the colour intensity of MitoSOX, a marker of ROS generation,  between control square and the HSe, high selenium square. These two:



















Control is essentially black, ie no ROS production and HSe is red, lots of ROS production. Let's cut out the intermediate LSe row and abutt the HSe to the control to make this as obvious as possible:



















Now I have another problem. The bright blue colour is an Hoechst stain developed to show DNA, ie it shows the nuclei. I would expect the same intensity of staining with Hoechst stain irrespective of exposure to selenium for 6 weeks or not. The control Hoechst stain is dull in the control while in the HSe image it is bright. Perhaps there has been a problem with the photography?



















I can help out by simply increasing the exposure factor for whole of the control row using the colour adjustment in Preview software. This is what it looks like:



















Which makes for an interesting comparison between the MitoSOX fields at this (???corrected???) exposure/brightness:



















I defy anyone to see any difference between the control MitoSOX intensity and the high selenium exposure MitoSOX intensity. Which makes the rest of the paper, attempting to explain this non-finding, of little value.

So what do I make of this table:




showing a clear dose response to sodium selenite supplementation in both bodyweight and fat weight? For someone who thinks that markedly reducing ROS in adipocytes should cause lipolysis this is exactly what you would expect.

Bear in mind that these rats were gavaged with selenium, it wasn't in the food, there is no "palatability" issue.

I think this is real. Why? Because I want it to be and because of this paper


which found exactly the same effect. This is food intake per week:











The results for weight gain are exactly as expected from the food intake and are given in Table 4, which is huge and turned on its side over two pages. You need a VPN and a line to a server facilitated from Kazakhstan or just take my word for it, food intake predicts final weight, this time.

This is explained away by the authors using ad hoc hypothesis number 12,352 thus:

"A reduced dietary intake was noted throughout the observation period for all treatment groups, which may be considered as a consequence of the unpalatability of the dietary mixture. This resulted in a decreased bodyweight gain in all treatment groups, particularly the females."

I guess, if you were dumb enough, you could call this "reverse Reward". No sniggering!

Combining parts of both papers leaves me deeply embedded in my own confirmation biases, which make sense, at least to me.

ROS are fundamental.

Peter

12 comments:

mct4health said...

Hi Peter, I don't think it's enough to think about mitochondria alone, it's the cooperation of mitochondria with peroxisomes, microsomes etc. that determines the total production of ROS.
Here I present my bias, with quite interesting pictures from a few studies, the links are below
https://mct4health.blogspot.com/2022/10/peroxisomes-torn-from-chain-how-to-tame.html

Jaromir

Eric said...

Threadjacking again:

https://www.ucl.ac.uk/news/2022/jul/famine-and-disease-drove-evolution-lactose-tolerance-europe

I think you had some comments on this paper but can't find it right now. Maybe I'm not remembering correctly?

Then there was this chance find:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916907/

Our study reported that total dairy food consumption was not correlated with LDL-C blood levels. However, multivariate analyses showed an inverse association between serum LDL-C and milk intake as well as a positive association between ricotta cheese intake and LDL-C concentrations.

Puzzling to say the least.

Lastly, did you see this?
https://www.youtube.com/watch?v=ZdiUnmpOgqE

940 nm light improves outcomes of those hospitalized for Covid pneumonia. Significance is striking. I am just not sure I can follow Dr. Seheult's explanations. He seems to say the IR light helps by supressing ROS signalling?!

mct4health said...

Eric, the milk by its calcium content prevents oxalate absorbtion and this could lower LDL-C. Oxalates probably play a big role in aterosclerosis.

karl said...

Ah selenium.. Another metal - another enzyme (or 3) that is part of thyroid metabolism. All three of the deiodinases are selenium-containing enzymes. Which makes me think that perhaps there was an earlier time when selenium WAS the enzyme to convert T4 => T3?

This garbage reminds me of another paper that claimed that selenium reduced thyroid production - but missed the idea that more conversion of T4 => T3 would lower TSH. Correlation/causation befuddlement everywhere I look in the literature these days.

Going further - these high level controls effect each other at every turn - if selenium pumps up T3, then you would expect a slight increase in MT activity which might end up with a bit more ROS? The paper didn't seem to monitor the T3 levels or even TSH? How in the world can they discount the effects of a change in T3 on MT function?

When I did a deep dive into Thyroid regulation I thought I would figure it all out, but then I found the list of things that effect thyroid regulation either directly or indirectly to be amazingly long - all sorts of feedback loops - nested - redundant etc. What Bret Weinstein might comment on as "Welcome to complex systems". (He should interview you someday).

Speaking of Weinstein - I'm am no longer thinking that these rat models are good science, they have abnormal telemer length to the point that most of them die of tumors unlike their wild counter parts - how might that effect this paper?

Eric said...

mct4: yes, but how do you explain that Ricotta cheese has the opposite effect. It's not like it was free of calcium...

cavenewt said...

Eric: ricotta cheese finding is "puzzling to say the least." That pretty much sums up a lot of correlative studies. Take them with a Volkswagen-sized grain of salt.

Re: Selenium. I know it's not scientifically relevant but it's interesting because there's usually a grain of factuality in episodes of House MD. One of the two plots in this episode is a CIA agent who's suspected of being the victim of an assassination attempt, but actually ate too many Brazil nuts. https://en.wikipedia.org/wiki/Whatever_It_Takes_(House)

Peter said...

Hi mct4heakth, absolutely. The problem is that peroxisome research is in its infancy and there’s not a lot to work with.

Eric, I’d be very cautious about clinically assessing lactose insufficiency without the absolute eliminations of mitogens which might present enterocytes at the brush border before lactase expression was adequately developed. That’s cereal grains and legumes…

Eric and cave, Observational nutritional studies, haha. And who gives a f*ck about LDL-C levels anyway?

Re video, wow. The guy is *quadruple* boarded. He is very, very good at passing exams. No time to listen at the mo but hopefully he has something useful here which I can get back to. I feel some caution because passing boards is no guarantee of insight/ability, just the ability to pass exams. I will still try and get a listen.

Eric, yes, thinking back through the loops and loops of evolution to the fossils of metabolism is the way to go. Today is the end product of probably 4,000,000,000 years of tinkering and overlaying. The core process will still be deep in there. Looking at the end system will be “tinkering overload”.

Peter

Eric said...

Peter,

yes, he's 4x certified and never seizes to rub that in. He is also very wordy but takes care to explain carfully for those not versed in the lingo. I have taken to watching his postcasts while folding laundry.

He presents good finds in terms of papers and stray from the gospel when light is concerned but even now keeps advocating boosters so his mind remains partially closed :)

Here's an update to that video. Towards the very end, he presents a study that shows lipd markers in Oxfordshire and Leiden as a function of the weather in the previous 7 days. Note to self: get and read study.

https://www.youtube.com/watch?v=BW_EtdPWmKM

Passthecream said...

Peter:

"absolute eliminations of mitogens which might present enterocytes at the brush border before lactase expression was adequately developed. That’s cereal grains and legumes…"

I believe you have solved the puzzle, it is cheese ON TOAST which confounds the observations!



LDL be damned.

Peter said...

Oops, that will be lactase, not lactose in my last comment. My bad.

Peter

raphi said...

Peter you said => "Eric, I’d be very cautious about clinically assessing lactose insufficiency without the absolute eliminations of mitogens which might present enterocytes at the brush border before lactase expression was adequately developed. That’s cereal grains and legumes…"

I said => "I strongly suspect most poor reactions to dairy can be fixed by moving immunogenic triggers, most notably grains" https://twitter.com/raphaels7/status/1614255091321810946?s=20&t=1rawsdAbEagtJGf0vosIBQ

cavenewt said...

"I strongly suspect most poor reactions to dairy can be fixed by [re-?]moving immunogenic triggers, most notably grains"

It worked for me.