Protons (80) Carpentier II

I've been wanting to write about this paper for some time. But it annoys me. A lot.

Increased postprandial nonesterified fatty acid efflux from adipose tissue in prediabetes is offset by enhanced dietary fatty acid adipose trapping

I only realised yesterday that it is from Carpentier's group. Clearly Carpentier is asking questions about subjects which I am interested in. So it's time to say something.

First comes the title. From my point of view it absolutely concurs with what I would expect. If we accept that people have impaired glucose tolerance because they have accentuated lipid release from adipocytes (due to increased lipid droplet size necessitating elevated basal lipolysis), then storing lipid after a meal *should* increase FFA efflux from adipocytes. Make them big, they then "leak" (in a very controlled manner).

Carpentier used a very comprehensive tracer study to show that this effect is real and does occur (though they didn't look at, and clearly don't have, an hypothetical mechanism). The other finding they report is that this rise in efflux is not from chylomicrons spilling FFAs when they dock with extracellular lipoprotein lipase. The excess FFA efflux comes from adipocyte intracellular lipolysis.

This is consolidated in the first sentence of the abstract:

"The mechanism of increased postprandial nonesterified fatty acid (NEFA) appearance in the circulation in impaired glucose tolerance (IGT) is due to increased adipose tissue lipolysis..."

Both of which confirm my biases. Which makes me want to like the paper.

Here's the fly in the ointment, also from the abstract:

"Plasma glycerol appearance was lower in IGT (P = 0.01), driven down by insulin resistance and increased insulin secretion."

So.

The group is saying that they have documented elevated postprandial FFA efflux from adipocyte lipolysis in subjects with IGT. But they have NOT detected a rise in glycerol from that lipolysis. Quite the opposite.

What's it to be? More lipolysis giving elevated FFA efflux, or less lipolysis giving less glycerol efflux?

You can't have both at the same time. In the abstract and the discussion they are claiming that hyperinsulinaemia secondary to insulin resistance is suppressing glycerol release. But not suppressing (accentuated) FFA release.

Go figure.

So I've sat on the paper, because it confirms most of my biases but doesn't make sense.

The paper is important because, if their FFA flux data are believable, what they are saying is that adipocytes of people with IGT are releasing FFAs in the post prandial period, but there is, at the same time, enhance uptake of FFAs in to adipocytes.

In my terms: accentuated basal lipolysis, which is protective of adipocytes from over distention, is being offset by FFA uptake by adipocytes as a consequence of enhance insulin and insulin signalling secondary to linoleic acid's inability to resist it.

It matters because there is a battle over adipocyte size. When excessive insulin signalling wins over basal lipolysis, people get hurt. Especially their adipocytes do.

The downstream effects are not pretty.

Peter