Beneficial effects of metformin on energy metabolism and visceral fat volume through a possible mechanism of fatty acid oxidation in human subjects and rats
Here are the RQ data from 16 healthy humans after an overnight fast and for the three hours following a mixed carbohydrate/fat meal tolerance test (type of carbohydrate and fat not specified).
Aside: Here is the test "food" description: "meal tolerance tests (592 kcal, 75g of carbohydrate, 28.5g of fat; Saraya Co., Osaka, Japan)". It's great to know that there is a company called Saraya and that they have headquarters in Osaka. But I can't even find out what sort of "meals" Saraya make. Quite how anyone might replicate this study using the methods section is beyond me. In addition to these omissions the test "meal" is repeatedly described as "cookies". Go figure. Still, let's assume the measurements of RQ is numerically accurate, fingers crossed. End aside.
These healthy people, who haven't eaten overnight, have an RQ of 0.8 and the test meal produced a downward trend in RQ indicating that the "cookies", providing roughly 50% of calories as fat, tended to increase fatty acid oxidation or decrease carbohydrate oxidation. I can't be arsed to criticise their stats methods. Let's stick with the gross changes.
After two weeks on metformin at an eventual dose rate of 500mg three times daily there is a significant fall in fasting RQ indicating an increase in non-fed fat oxidation compared to the control state.
Under metformin the "cookies" produce a rising RQ, suggesting preferential metabolism of glucose in the immediate post prandial period.
So metformin promotes fat oxidation during fasting but promotes glucose oxidation during the first three hours after a plate of "cookies".
Interesting.
We should see if we can explain these effects on RQ in terms of mitochondrial glycerol-3-phosphate dehydrogenase (mtG3Pdh), electron transporting flavoprotein dehydrogenase (ETFdh) and the redox state of the CoQ couple driving reverse electron transport (RET) through complex I.
Peter
Not sure, but I think the "meal test" is the same or based on this one: https://www.jstage.jst.go.jp/article/endocrj/53/2/53_2_173/_article
ReplyDeleteLooks like it might be. Obviously ABILIT corp have been bought out by Saraya, also of Osaka, or simply re named themselves without moving head office... At least we can now guess whether the MCT component in the butter was responsible for the fall in RQ in the non-metformined state. Or whether saturated fat naturally increases fat oxidation, possibly by allowing the body to resist the action of insulin????? That might be interesting.
ReplyDeleteThanks!
Peter
Hi Peter,
ReplyDeleteI believe these effects would be consistent with the GLP1 increase from metformin; this favors insulin & glucose oxidation postprandial (when you need it ) but ampk and ppara induction attendingly favors superior fat oxidation fasting.
Hi Wooo,
ReplyDeleteI'm still thinking at the very basic signalling level within mitochondria/cells. I'm also (somewhat archaically) still wedded to the primacy of insulin over other signalling molecules so I haven't really looked at GLP1. You are way ahead of me there. I still haven't even started reading about leptin yet!!! And now I'm looking at insulin induced insulin resistance. Blocking the initiation of insulin signalling at basal levels during fasting would give better fat oxidation and blocking insulin induced insulin resistance at post prandial insulin levels to allow continued glucose oxidation after a meal. Assuming that RET is real and is driven by mtG3Pdh summating with complex II and ETFdh to reduce the CoQ couple......
Peter
Hi Peter,
ReplyDeleteI find your work important; even if I sometimes have difficulty with all the details – but that is not the important part
What is important, I recently stumbled on a study which might interest you:
"Gluconeogenesis during endurance exercise in cyclists habituated to a long-term low carbohydrate high-fat diet"
Don't know if you have seen it (you probably have), but just in case you have not see it, here it is:
https://www.researchgate.net/publication/296055925_Gluconeogenesis_during_endurance_exercise_in_cyclists_habituated_to_a_long-term_low_carbohydrate_high_fat_diet
It contains some respiratory measurements, which might interest you.
And furthermore, it contains this quote:
"…it is possible that participants in the LCHF group were drawn towards their diet because they were particularly suited to it."
Anyway…
Speaking of self-selected LC followers, I recently had to come to the conclusion that I have most likely some sort of inborn error of carbohydrate metabolism, possible some sort of Glycogen Storage Disase like late-onset McArdle or late-onset Tarui (if not some of the more exotic GSDs like GSD9D…).
So I was looking through Wikipedia, all the while adding links and so forth, as I learned more about the topic – mainly for my benefit, but also with the hope it will help those who are affected by these diseases (hopefully adding studies about the benefit of LC nutrition where I can, like e.g. "Can a Low-Carbohydrate Diet Improve
Exercise Tolerance in Mcardle Disease?" which I must add).
But it was all "the wrong way round", I needed a overview of glycolysis, and the diseases that are caused by problems in it. So I started this (which I will move to the appropiate wikipedia page):
https://en.wikipedia.org/wiki/User:Tony_Mach/inborn
When I came to Aldolase, I decided to look at all the forms of Aldolase (for the LOLZ, as the young people say), and gosh, Aldolase C is interesting. What if these disease are carbohydrate metabolism diseases?
Surely, the Aldolase C bit is "tentative" at best. Obviously I am biased, I see carbohydrates as evil everywhere. And I will not add to Wikipedia proper.
But still, makes me think.
I will continue this, put a "sanitized" version on Wikipedia proper – but keep this tentative version with everything I find.
(I guess I read these type of speculations somewhere before, possibly on your blog here – so apologies that I do not give proper credit for where I read this first)
^ Its the peroxisomes that are arguably providing additional substrate in such scenarios via medium chain fats and ACoA. Fasting and exercise promotes PPAR alpha . . . It is entirely logical that peroxisomes play a significant but underrated role in energetics.
ReplyDeleteMetformin appear to be accompanied by improved catalase related function, which if the case is going to have multiple downstream implications .
https://www.ncbi.nlm.nih.gov/pubmed/24717679
https://www.hindawi.com/journals/omcl/2016/6978625/
A few people with DM2 (on diabetes.co.uk/forum/) have reported that the "dawn phänomen" seems to be reduced for them while taking Metformin.
ReplyDeleteI expect the effect of metformin on the liver needs to be considered in understanding the effects of metformin on other cells.