Saturday, February 08, 2025

Synchronicity and the origins of Protons (2)

This is the paper which Amber mentioned in her podcast conversation, primarily in the context that low carbohydrate, high fat diets markedly reduce hunger in diabetic rats. I wasn't looking at that aspect, what had caught my attention was the caloric intakes of the non diabetic rats on different levels of linoleic acid inatke and I had this post pretty well complete. Which looked pretty uninteresting unless you have a Protons perspective. Here's the post very much as was:








I happened on this paper by Edens and Friedman many years ago:

Response of Normal and Diabetic Rats to Increasing Dietary Medium-Chain Triglyceride Content

and this is the core quote:

"On the other hand, LCT-fed [corn oil, 55% linoleate] normal rats overate for several days when they were given the higher fat diet."

Notice the word "overate" and that this was transient, then look at Figure 5, from which I've removed section B because that is just about the diabetic rats which are irrelevant to the current discussion:
















I think it is not unreasonable to draw a straight line through the calorie intakes, provided we ignore the upper trace of the corn oil fed rats (filled dots) in the section circled in blue, which are the ones we are interested in:
















NB the line trends downwards because the rats are slowing their growth rate so need fewer calories per day as the weeks go by.

Next we can look at the blue circled area and add in, by eye on Powerpoint, a smoothed line for the calorie intake during this period. Which looks like this, again in blue:















The 25% fat by weight diet supplied around 43% of calories as corn oil which gives around 24% of calories as linoleic acid.

We've seen something similar before of course, from the Schwartz lab:


















on to which we can draw a similar set of lines:



















I think exactly the same phenomenon is happening in both diets, one from 1984, the other from modern day D12942. The effect is much smaller and goes on for half the time period but it's there. These differences give us some insight in to what has been tweaked over the decades to improve the obesogneic nature of diets leading to the development D12942 and D12451.

Aside: The reason why the effect is small and the effect of MCT oils is minimal is another whole discussion. On the to-do list. End aside.

Is the 25% fat diet from 1984 going to be obesogenic when the rats only "overate" for a few days? Of course it is. Rats on D12942 only over eat for seven days before food intake drops to statistically indistinguishable from chow fed rats, but they still get slowly fatter over the weeks. So too would the rats in this venerable study, had they eaten it for long enough. IMNSVHO.

The discussion section is interesting because the authors are continuously trying to tease metabolic effects apart from "palatability" effects. That's good but the lack of concepts that insulin signalling is a redox based system and that the generation of superoxide/H2O2 is controlled by the relative proportion of FADH2 and NADH produced by a given metabolic substrate means that the conclusions must, necessarily, be far from complete.

So it lacks the Protons hypothesis and cannot tease out why a jump in linoleic acid intake causes a brief period of "overeating". And, of course, if you considered these few days of significantly increased caloric intake to be the only effect of the high fat corn oil diet you might be forgiven for concluding that polyunsaturated fats are non obesogenic The authors published in 1984 so cannot be criticised for being unaware that the redox state controls caloric ingress in to individual cells, as falls out from the appreciation of the ratio of FADH2 to NADH from fats vs carbohydrate as they affect the function of the ETC, RET and superoxide generation. Especially the effect of sub-physiological production of FADH2 per unit NADH as it features in the beta oxidation of linoleic acid.

Where as the difference in redox signalling generated by linoleate vs stearate (and to a lesser extent palmitate) has good explanatory power.

Peter

No comments: