That big belly of yours is on fire if you have type 2 diabetes

belly on fireIf you’re sporting a pot belly, you probably think it is a giant sac of very full fat cells, but this is not quite true.

It is true, a big portion of that belly is filled with rather unhappy stuffed to overflowing fat cells, specifically the white kind, whose job it is to store all those extra calories you routinely gather, for a rainy day.

But, because of their continuous whinging and whining, tucked in among the fat cells packing the belly, are lots and lots of macrophages.

Researchers from Stanford University School of Medicine think it is the marcophages, not the fat cells, that are the problem in type 2 diabetes.

The gene at the centre of the haystack

The team of scientists have spent years trolling through public genetic data bases, in the search for clues behind the pathology of type 2 diabetes.

The systematic search brought the CD44 gene onto their radar. In the 130 gene-activity-level experiments involving diabetic tissues included in their mining operation, 78 showed CD44 expression levels were a lot higher in diabetic tissues.

The problem with this gene is not that it is defective so to speak, but it is definitely excessively busy, in the type 2 diabetic fat tissues, irrespective of whether the tissue is rat, mouse or human.

Macrophage gene turns traitor in type 2

So the big question – what does CD44 do ?

First off, the gene is not found on fat cells, it is a gene associated with marcophages, which are cells that form part of the body’s armed response unit. The CD44 gene makes a protein which is found on the outside of marcophages.

This CD44 protein on the outside of the macrophage is able to hook up with a special receptor on the fat cells – so this explains the fat-macrophage connection. It also brings us back to the beginning – big bellies are a collection of upset fat cells and marcophages.

And big bellies are the beginning of type 2 diabetes.

Uncovering the armed response at devcon 5

The Stanford team looked for answers in genetically modified mice, specifically, they ran a few experiments on mice that were missing the CD44 gene, so called “CD44 knockout” mice. The strain of mice they used in their studies, are typically porky with a high propensity to become diabetic when fed too much.

They started overfeeding these “special” mice, expecting to turn them diabetic, with the continuous high calorie diet. The normal mice got tubby and became insulin resistant, but the mice without the CD44, just became fat – they never developed diabetes. The blood sugar levels remained perfectly normal when the CD44 gene was missing.

The CD44 seemed to be the link between obesity turning into something beyond excess wobbly bits. CD44 receptors are involved in creating devcon 5 levels of inflammation in the fat cells.

Putting a muzzle on CD44

Looking to confirm this connection between macrophage infiltration and fat cell inflammation, the team tried a different experimental approach. They created a muzzle for the CD44 receptor by injecting an antibody designed to bind to the receptors, so they can’t work properly.

Again they fed their mice extra calories, in the form of a high fat diet. As expected the mice became diabetic, but when the antibody was injected, things changed. Blood levels dropped to normal ranges within a week. The mice remained fat, but the number of macrophages in the animal’s fat tissues dropped.

Muzzling the CD44, stopped the excessive inflammation and normalized sugar levels.

Hush that inflammation

The Stanford team will be working hard to turn this discovery into a medicine that crushes CD44 in one way or another. But it will take years before such a medicine makes it to the shelves of your pharmacy.

But, the message is clear – you big belly is on fire. The bigger the flame and the longer it burns, the bigger your future health troubles.

Lowering sugar levels is not enough, you’ve got to smother the flame through better body chemistry.

Getting the 7 Big Spoons sorted is a good place to start……. 

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Balance Eicosanoids Rein in insulin Dial down stress Sleep ! Increase Vit D Culivate microflora Think champion
 
Expression-based genome-wide association study links the receptor CD44 in adipose tissue with type 2 diabetes. Proceedings of the National Academy of Sciences (2012) 109(18):7049-7054.  K. Kodama, M. Horikoshi, K. Toda, S. Yamada, K. Hara, J. Irie, M. Sirota, A. A. Morgan, R. Chen, H. Ohtsu, S. Maeda, T. Kadowaki, A. J. Butte.
 

Interested in learning more about the chemistry behind type 2 diabetes ?

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Further reading

eskimo eating fish fat cell drinking milk pollution smokes out the heart
The side effects of obesity stopped by omega-3s Give your fat cells a bottle to pacify them The face of pollution inflames the soul

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