What effect does saturated fat (palmitate) have on muscle insulin sensitivity?

“The saturated fat palmitate, when exposed to muscle cells, reduces their insulin sensitivity – said differently, it increases insulin resistance. The evidence shows that palmitate increases reactive oxygen species production, DNA damage through breaks in the DNA strands that are necessary for cell survival, and inevitably increases in the susceptibility for cell death. This, however, is not translatable based on the evidence shown here, because the concentrations, environment, and other factors make it impossible to translate toa real world scenario; although, this research at least indicates that palmitate is harmful for muscle cell function, even if the magnitude can’t be determined.” I’ve been reading quite a few studies on the topic of insulin resistance and the role different fats have on it. In this piece, I’d like to highlight just a few studies [Figure 1] that probed the question “how does fat affect muscle insulin sensitivity?” – with a special emphasis on the most abundant saturated fat - palmitate. This is important, because muscle sucks up, in an absolute sense, the most blood sugar, and therefor has the greatest role in regulating our metabolic health regarding protecting us from diabetes. So, without further ado, let’s look at some studies.

What is muscle insulin sensitivity?


Muscle insulin sensitivity can be explained as the reaction that occurs within the muscle cells when insulin binds to its receptor embedded in the muscle cell membrane. Meaning, when blood insulin attaches to the insulin receptor that is found on the surface of the muscle cell, there is a cascade of reactions within the muscle cell that allow the muscle cell more blood sugar into the cell. This, in turn, reduces blood levels of sugar as the sugar is now being shuttled into the muscle cell. The fewer insulin molecules are necessary to enact this event (sugar shuttled into the muscle cell), then the more insulin sensitive the muscle. How does saturated fat (palmitate) affect muscle insulin sensitivity?


As I mentioned, I’d like to focus this discussion on the saturated fat palmitate, which is the most abundant saturated fat in our food. So, then, how does palmitate affect insulin sensitivity of muscle? It turns out, it likely reduces it.



If we turn our attention to this first piece of data, wherein the researchers cultured rat muscle cells in palmitate and then measured their ability to take up glucose, there was a noticeable lack of sensitivity in the cells exposed to palmitate when they were introduced to insulin, which would normally drive up the uptake of glucose (as seen in the C – Control/No Fat condition) [Figure 2]. It would easily be argued by someone with a sharp eye, based on this data, that the basal levels of glucose/sugar uptake are higher in the palmitate, however. This seems true at first glance, because the statistical analysis is misleading and indicates no difference, but that’s likely because an analysis was not performed between the control basal glucose uptake and the palmitate glucose uptake. However, other measures that I’m not showing here do show several lines of evidence that palmitate follows the first conclusion over the second (namely, that palmitate reduces glucose uptake and causes insulin resistance/insensitivity).


Okay, but these results were in rat muscle cells, does it also apply to human muscle cells?


The answer is yes, with a caveat, but we’ll leave the caveat for later in this article. Palmitate given to isolated human muscle cells also showed reduced uptake of glucose [Figure 3].


It should be noted that these studies are performed on isolated cells, known as in-vitro experiments, so the carry over is low. I would also add that I wouldn’t even pretend to argue that our cells are exposed to the same concentrations of palmitate as those used in these studies. So, while this evidence indicates a harmful nature of palmitate on muscle insulin sensitivity, it does not indicate the severity, or even a complete picture, of that harm. Why does saturated fat (palmitate) affect muscle insulin sensitivity?


There are a number of mechanisms. One, palmitate increases reactive oxygen specie generation [Figure 4] – meaning, more harmful versions of the oxygen molecule are produced within the muscle cells. This, in turn, damages the muscle cell, impairing its ability to signal insulin binding to it. Certainly, there’s added nuance here, but I’m not writing an essay.


This reactive oxygen specie generation also goes hand in hand with added genetic damage [Figure 5]. The data also shows that if palmitate is used on the cells, the cells incur substantial DNA damage – which, of course, leads the entirety of the cell to suffer as it can no longer produce the requisite proteins for its own survival, and it just so happens that the muscle cells are more prone to dying, as well. Interestingly, if the DNA is repaired, the cells produce less reactive oxygen species, and are also less prone to cell death.


The mechanisms extend into caspase cleavage, JNK protein activation, ceramide synthesis, and more, but again – I’m not writing my thesis right now. If you’re part of the Physionic Insiders, you will have access to me and my other content discussing all this in significant depth.

Conclusion


The saturated fat palmitate, when exposed to muscle cells, reduces their insulin sensitivity – said differently, it increases insulin resistance. The evidence shows that palmitate increases reactive oxygen species production, DNA damage through breaks in the DNA strands that are necessary for cell survival, and inevitably increases in the susceptibility for cell death. This, however, is not translatable based on the evidence shown here, because the concentrations, environment, and other factors make it impossible to translate toa real world scenario; although, this research at least indicates that palmitate is harmful for muscle cell function, even if the magnitude can’t be determined.


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