This post is a slight aside based on minor details in the paper "Insulin resistance is a cellular antioxidant defense mechanism". Which shows, quite clearly, that palmitate at levels as low as 0.05mmol/l causes some degree of insulin resistance. By 0.15mmol/l it's significant and by 0.5mmol/l it's worse. The graphs are from myocytes in cell culture.
This graph show GLUT4 count on the surface of myocytes. Left is control, next is the count after an acute exposure to insulin, taken as the 100% response. Adding more and more palmitate decreases the percentage response.
No one, not even a fatphobic vegan, has palmiatate levels in the FFAs of their blood as low as 0.05mmol/l.
This graph shows the effect of exposure time to 0.15mmol/l on GLUT4 translocation. Things get worse by the hour. Is this real?
Let's have a look in the methods:
"Palmitate (PALM) treatment was performed essentially as described in ref. 5"
So let's go to ref 5:
5. Hoehn KL, et al. (2008) IRS1-independent defects define major nodes of insulin resistance. Cell Metab 7:421–433.
In results we get this superb snippet:
"In our preliminary investigations, we observed that high (>300 μM) palmitate doses were toxic to cells, resulting in morphological changes and even detachment from the substratum."
Palmitate is clearly pretty nasty stuff. And I feed it to my daughter!
In the methods section under "Oxidative stress" we get a description of "stepdown medium", as used in both of the studies discussed. The composition of cell culture medium may be common knowledge to people using cell culture for a living but it was news to me. This is virtually a throw away comment:
"...while total glucose levels (measured with an Accu-Chek II glucometer [Roche]) decreased slightly from 24.7 ± 1.6 mM to 23.3 ± 1.9 mM".
The DMEM cell culture medium used here contains 25mmol/l of glucose!
So let's rephrase that toxicity of palmitate:
"Palmitate at 0.3mmol/l is severely toxic to cultured cells in the presence of 23mmol/l of glucose".
That I can certainly believe.
Aside: It is very interesting to note that palmiate at 0.15mmol/l is low-physiological for a human and yet is described as toxic, without mention of the grossly pathologic 25mmol/l of glucose in the culture medium. I suspect that whenever you look at a cell culture based study demonstrating palmitate toxicity this will apply.
So, does palmitic acid cause insulin resistance (aka superoxide production) under low glucose conditions? Where there is no caloric overload?
Studies looking at palmitic acid in the presence of low glucose are as common as hen's teeth...