Saturday, November 04, 2017

Metformin (04) Pre and Post Prandial

The next metformin paper to look at is this one:

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".


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.



Nicolás Flamel said...

Not sure, but I think the "meal test" is the same or based on this one:

Peter said...

Looks 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.



ItsTheWooo said...

Hi Peter,
I 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.

Peter said...

Hi Wooo,

I'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......