I've been thinking quite a lot about the difference between subcutaneous adipocytes and visceral adipocytes. The difference appears to be much deeper than location, though that matters. The next paper is one of those terribly clever research projects where enormous amounts of information is accumulated but little integration or understanding seems to take place. Here it is:
Differential response to caloric restriction of retroperitoneal, epididymal, and subcutaneous adipose tissue depots in rats
One problem is that they are trying to do too much, so just ignore any of the bits about caloric restriction (CR) which creep in to the butchered graphs. All I'm really interested in is ad-lib (AL in the graphs) fed mice and their adipocytes. I want to know about normal insulin signalling. Here are the fed and fasted insulin levels from those mice. Fed on the left, fasted on the right, part of Table 1:
The dollar signs denote statistical significance (not paydirt). Next are excerpts from Figure 5. I've cropped out the bar graphs showing the pAKT levels from fed and fasted mice. The group is using pAKT as a good marker of insulin signalling. First here's the SC (sWAT) graph:
We only need to look at the AL group. There is a fed insulin of 1549.76pg/ml supporting the reference level of insulin signalling. Next to it we have the fasted level of insulin signalling, somewhere around half reference value. This is being supported by a plasma insulin level of 477.25pg/ml. Simple. More insulin, more pAKT, more insulin signalling. It seems reasonable to consider that the fed insulin level supports lipid storage in subcutaneous adipocytes and that half this level (fasting) might allow lipolysis. We can ignore the CR group.
Here is the same graph from a sample of retroperitoneal adipocytes:
Here we have, again, the level of insulin signalling supported by a fed state plasma insulin of 1549.76pg/ml as reference and just look at the level of insulin signalling being supported by the fasting insulin level of 477.25pg/ml. It's no different to the fed level of signalling. Hmmmmm.
So, theoretically, most of the fat loss under fasting should come from the subcutaneous adipocytes. We need to go back to Table 1 for that:
There we go, the tissue with the least fasting insulin signalling (sWAT) loses over four times as much lipid as the tissue where insulin signalling is maintained at the lower (fasting, 477.25pg/ml) insulin level (rWAT).
This looks very much like one of the intrinsic differences between subcutaneous adipocytes and visceral adipocytes is that visceral adipocytes maintain insulin signalling at much lower levels of plasma insulin than do subcutaneous adipocytes. You have to store calories which arrive without insulin somewhere. Looks like this is the place!
I'm interested in this because I want to know why VLDLs, released from the liver following lipid overload (from fructose DNL, alcohol DNL or inappropriate FFA release from adipocytes under fructose or alcohol) end up in visceral adipocytes. We know these VLDLs are only released under low insulin levels (that was a long time ago!) and this current paper tells me why the VLDL lipids end up in visceral adipocytes. It's not an address technique, it's just that visceral adipocytes are programmed to store fat under relatively low insulin levels. To get decent lipolysis from visceral fat I suspect that you need really low insulin levels, something a bit like those of ketogenic diets. Well, what do you know...
What is it about the visceral adipocytes that programs this?
Perhaps we should look at IGF-1 for the answer to that one.
EDIT We don't know the absolute level of signaling in either the sWAT or rWAT tissue. Fed is taken as reference and fasted is shown as the percentage change from the fasted state. The reference value may differ between the two depots. Just needs bearing in mind. END EDIT
Friday, March 02, 2018
On phosphorylating AKT within visceral fat
Posted by Peter at Friday, March 02, 2018
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Thanks for that analysis.
You're welcome bill
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