Foie Gras (6) inflammatory mRNAs

 Okay, time to look at this study

A High Linoleic Acid Diet does not Induce Inflammation in Mouse Liver or Adipose Tissue

It presented itself to me while I was looking  for explanations as to why linoleic acid was or wasn't inflammatory in hepatocytes. Being "inflammatory" is determined, here, by the response of treating freshly isolated cells, in this case macrophages, to incubation with linoleic acid at 50 μmol/l for 12 hours, in addition to the normal culture medium. Some ferreting around on the internet suggests that the culture medium used, when fresh, contained glucose at 33 mmol/l. The concentration of LA, 50μM, is low and physiological for a FFA concentration under hyperglycaemia. The macrophages were assessed for expression of pro-inflammatory genes coding for these proteins:

Monocyte Chemoattractant Protein-1 (MCP-1)

Macrophage inflammatory protein-1 (MIP-1)

F4/80 is a gene for the surface marker of macrophages

and good old TNFα and Il6 get thrown around too.

We can ignore the anti-inflammatory gene expression Ym1 and Ym2.

This is what they found for pro-inflammatory gene mRNA relative expression, linoleic acid is tall hatched bars. It's a log scale:

So we can say LA is pro-inflammatory in this model. No one in obesity research wants to find that the cardiological darling and cholesterol lowering PUFA are pro-inflammatory. I told you they were rank amateurs. Anyway, they developed another model, in-vivo this time, which got the correct results.

They fed the mice the diets I mentioned in the last post for four weeks then looked at pro-inflammatory gene expression in both white adipose tissue and liver tissue immediately after euthanasia.

This was much more satisfactory. In both tissues the high PUFA diet was not inflammatory, with a trend towards it being anti-inflammatory in adipose tissue:

Adipose, from Fig 2:

and liver from Fig 3:

However, there is another snippet of information also available in Fig 3. The activity of myeloperoxidase system tells us slightly more than the relative mRNA for inflammatory genes do in the bulk of the figures. Myeloperoxidase tells us whether the WAT cells in Fig2 are actually using the pro inflammatory genes to produce inflammation. This is what they found. The chart is split in two because the HF (high fat diet, something like D12492) was so activating it was an order of magnitude higher than all of the others, so needed it's own scale:

I think we have to be very, very careful about what we mean by "inflammation". In fact I might just take a brief pause here and explain what I think "inflammation" means, before running through what is happening in this study. That may need some cellular physiology rather than mitochondrial physiology.

Here's my conundrum:

CVD is an "inflammatory" condition, sic.

The most potent anti-inflammatory agents available to modern medicine are the corticosteroids.

Corticosteroids make CVD much, much worse.

Somebody, somewhere, has an odd idea about what "inflammation" might be.

With apologies for the hiatus.

Peter