Saturday 26 April 2014

Fat Digestion explained

Here is a lovely text detailing how fat digestion is handled.

Its worth reading the entire text but in summary ....

1 )  Eaten fat ( triglycerides ) is acted on by lipases in the GI-tract which split it into free fatty acids.

2 ) free fatty acids are absorbed by the enterocytes  ( cells of the GI tract )

3) enterocytes partition the fatty acids into different fate's, one of which is package onto a chylomicron

4 ) the chylomicron's are released into the systemic circulation where they float around and eventually interact with lipo-protein lipase in the endothelium of the various organs, one of which is adipose tissue. LPL then begins to break down the triglyceride from the chylomicron's into free fatty acids.

5 ) the presence of chylomicron's in the adipose tissue blood vessels also stimulates the release of ASP, acylation-stimulating protein  from adipocytes, which helps shuttle free-fatty acids liberated from chylomicrons by LPL into the adipocyte.

6 ) free-fatty acids that not are shuttled into the adipocyte escape and enter the systemic circulation, where they become part of the serum FFA pool. This contribution can be anything from 5-35% of the total serum FFA concentration.

7 ) once inside the adipocyte, free-fatty acids are once again packaged up into triglycerides, and are assembled into small lipid droplets in the endoplasmic reticulum.

8 ) the smaller lipid droplets are then acted on by lipid droplet proteins like FSP27 which fuse smaller lipid droplets into larger ones, eventually combining them with the large central lipid droplet present in the adpiocyte, at which point the fat can now be considered "body fat".

You should of noticed by now that there was no mention of insulin anywhere. So yes, dietary fat can be stored as body fat "without" involving insulin. But its worth noting that the stimulation of ASP by chylomicron's is enhanced in the presence of insulin ( link )

I expect that in the absence of high insulin levels, more of the fatty acids liberated from chylomicron's "spills" over, escaping adipocyte trapping and entering the systemic serum FFA pool. I remember from one of peter's post he mentions that high serum FFA = high energy expenditure, provided ofcourse again we keep insulin low since insulin inhibits fat oxidation.

So at this point one must be wondering, does this mean eating lots of fat and calories even without insulin stimulating carbs, we can get obese? I have doubts about this. The fact that chylomicron's stimulate ASP ofcourse is the ultimate evidence that we dont need ( elevated ) insulin to store dietary fat as body fat. The problem is this..... obesity is so much more than just "excess" triglyceride stored in adipocytes. I think all we can say is that eating alot of fat and calories will likely result in a *bit* of weight gain, as sam feltham proved.

Indeed I do not know of any studies of over-feeding keto in normal lean humans, only to follow them up several years later and find they maintained the elevated fat mass and are resistant to weight loss, both key features of the "obesity " phenotype.

Also of mention is that, although chylomicron's directly stimulate fat storage via ASP induction, researchers do not use chylomicron's in culture when attempting to cause preadipocytes to differentiate into mature adipocytes. They do however, use insulin and glucose.








2 comments:

  1. Nice analysis.

    Has your scouring of the literature included cellular mitochondrial heterogeneity & segregation (resulting from the zygotic 'bottleneck') as possibly affecting acetylation patterns (due to the need to adjust energy thresholds in a tissue-specific manner)?

    I'm thinking of this in terms of how some people accumulate fat predominantly on their belly, compared to say, their butt.

    Thanks!

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    Replies
    1. Accumulation of fat in different fat depots has to do with genetics and hormones. See twin overfeeding studies.

      body fat from different areas of the body responds differently to different hormones. this means that adipocytes from different fat depots and inherently different.

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