Saturday, March 03, 2018

On phosphorylating AKT in visceral adipocytes under starvation

I was hoping to ignore the CR mice in the paper

Differential response to caloric restriction of retroperitoneal, epididymal, and subcutaneous adipose tissue depots in rats

but I don't think I can do it. OK, here we go.

Below are the same images as in the last post showing phosphorylation of AKT as a marker of insulin signalling. The fed CR mice have an insulin level of 1787.84pg/ml, pretty much the same as the fed AL mice (1549.76pg/ml).

Let's look at subcutaneous adipocytes (sWAT) first.

The fed level of plasma insulin is supporting twice the level of insulin signalling in the sWAT from a starving mouse as it is in an ad lib mouse. An adipocyte from a starving mouse  is more insulin sensitive than one from a plump mouse. Not unexpected and clearly the adipocytes are small and desperate to have more fat.

In the fasted state the plasma insulin is much lower in the CR mice (224.56pg/ml) vs fasting AL mice (477.25pg/ml) and this low insulin level supports the same degree of signalling in the fasted CR mice as the higher value in the plump but fasted mice. Again CR adipocytes are more insulin sensitive.

Next is the situation in retroperitoneal visceral fat (rWAT). Any value of plasma insulin between the AL fasted of 477.25pg/ml and somewhere around 1500pg/ml of either AL-fed or CR-fed state gives very similar levels of insulin signalling. Maybe a little higher in the recently fed CR mice:

But when we get down to the CR fasting insulin level of 224.56pg/ml we actually have significantly reduced insulin signalling in the visceral adipocytes of starving mice. A drop in insulin signalling is synonymous with increased lipolysis in adipocytes. Accessing visceral fat really does happen, but only at very low insulin levels.

Does this show in fat depot size? Not really. The fall in subcutaneous fat volume is there but the fall in retroperitoneal fat is minimal. Bear in mind these guys are dissecting out very small tissue depots. If you look at the histology/computer image analysis derived values for adipocyte size you can see that the CR visceral adipocytes do really shrink and this might even achieve statistical significance. It's the two columns at the right we're looking at:

Pretty much the same thing happens  in the subcutaneous adipocytes but we get no asterisks for the changes here. It's possible the visceral adipocytes might shrink more than the subcutaneous adipocytes, if you are hungry enough:

So I think it is reasonable to assume that lipolysis in visceral adipocytes becomes real at plasma insulin levels somewhere between 477.25pg/ml and 224.56pg/ml. To achieve this in a mouse needs a combination of long term caloric restriction plus total fasting for about 24 hours. At this plasma insulin level it is even possible that their rate of lipolysis exceeds that of subcutaneous adipocytes but that might be stretching the data even further than I have done already. Under normal mouse husbandry conditions visceral adipose tissue is there to stay. It won't release FFAs unless the adipocytes get so large that they leak some FFAs in the presence of insulin signalling.....

OK, I'll try to leave those poor starving mice alone now.



Eric said...

Hmmm, this is a case where people might be different from mice. Beer bellies have been known to shrink just from calorie restriction (or from LCHF) without the need for 24 h total fasts.

Peter said...

Wait for the next post Eric!

Peter said...

Actually, chronic caloric restriction (Weight Watchers) was reputed to drift people in and out of ketosis, especially in the mornings. Ketones are a pretty good surrogate for hypoinsulinaemia (MCTs excepted). Back around the turn of the century this was used in defence of LCing against the stupidity of OMG you're in ketosis. Yep, like anyone on WW........ Just a bit more consistent. And, boy, does ketogenic eating drop central obesity.


Eric said...

Yes, pushing keto, be it through fasting, CR or ketogenic eating, will melt central fat. My point was that those 24 h or longer total fasts are not needed.

Looking at your newer post, they certainly do help, but they are not needed.