Tuesday, 1 May 2012

Serum FFA Paradox - AGAIN!

Sorry if this post is a bit technical

haven't figured out the cause of increased serum FFA in obese people yet, anyway, that's for another day.

Here is a paper that offers a novel idea as to why a drop in serum FFA makes me feel energetic, as per the initial stages of the niacin flush.

If im reading it correctly, what this paper is basically saying is that increased serum FFA promotes lysosomal destruction of the lipid droplets in the AgRP neurons in the hypothalamus, this in turn provides substrates for the generation of ATP which in turn increases activation of the AgRP neurons.

Further, increased activation of AgRP neurons produces more of the Agouti-related protein which blocks the MC4R receptor, thus reducing energy expenditure and increasing appetite.

phew!, you still there?

side notes

  • FFA taken up by the AgRP neurons are preferentially esterified into triglyceride and shunted into lipid droplets
  • Wikipedia says it has been found that obese people have increased AgRP
Increased AgRP and serum FFA is a marker of starvation. This is exactly as I was saying before that it kinda looks like obese people are "stuck" in the fasting state, unable to transition to the fed state properly.

For years I was in denial about the existence of something which people would refer to as "starvation mode", where it was purported that voluntary calorie restriction would seemingly put you in this state whereby metabolism was down and fat storage was enhanced. I now see that perhaps there is truth to this afterall, as increased AgRP and NPY do exactly that, they decrease metabolism and increase fat storage + insulin resistance.

Where-as AgRP and NPY act as short term signals of starvation, Leptin deficiency seems to act more as a long term signal, informing your brain of when your fat cells are severely atrophied.

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