The Full Physiological Regulation of Fat Tissue ~ Part I of ?

Look it's late 2011 we have a disorder of excess fat accumulation, and low carb shills are saying that the physiological regulation of fat tissue by hormones secreted by the fat itself is irrelevant.  
~CarbSane channeling her favorite science fiction journalist/author

In this series of who-knows-how-many posts, I'm going discuss the full physiological regulation of fat tissue.   This was prompted by the response of the original LC Internet Kindergarten Cop to CICO vs. Regulation of Fat Tissue ~ Questions for Gary Taubes.  In that post I posed the following question:

  How can any hypothesis on the regulation of 
fat accumulation not include ASP and leptin? 

Indeed Taubes himself acknowledges the plethora of hormones in WWGF.  Note:  It's very easy to imagine how they can be so disturbed so that too much fat gets in and not enough gets out. {click to enlarge} 

Now, never one to disappoint, the LCIKC fired back with his supposed "gotcha" email exchange with Keith Frayn.  I will address that apparent "case closed" in more detail in a future post.  First I'm going to lay some groundwork discussing not only ASP and leptin, but some other bioactive peptides secreted by fat tissue, collectively known as adipokines, and their roles in both the local metabolism in the fat tissue itself and actions on remote non-adipose tissues/organs.  Still, I don't want to leave something like that just sitting out there unanswered.  This was the impetus for what I suppose could be considered a preface to this series:  Of Microscopes & Myopic Hypotheses.   Basically, I'm unwilling to believe Keith Frayn has gone senile or lost touch with advances in the understandings of dysfunctional fat metabolism.  After all, around the time of the aforementioned email exchange (Feb. 2011), Frayn was a contributing author of Secretion of adipokines by human adipose tissue in vivo: partitioning between capillary and lymphatic transport, published online less than a month ago.   Here is what Frayn wrote in his 2010 Ed. of Metabolic Regulation (screenshots from Google books, click to enlarge):

It is indeed unfortunate, IMO, that Frayn does not include ASP in his figures on p. 131 and 134.  However when one looks at his work looking at postprandial chylomicron triglyceride derived fatty acids, it seems he's referring to the triglyceride/fatty acid cycle in the post-absorptive state (from several hours post meal until termination of the fast).  Because it is indisputable that the TAG/FA cycle is highly perturbed in advance of, and upon the arrival of, chylomicrons on the adipose tissue scene, and that ASP plays a key role in the clearance and esterification of diet-derived fatty acids.  See here, here, here and here.   

Back to laying some groundwork.  The first piece of that I'd like to lay is just adjusting a mindset.  I've long felt that Taubes' popularity is such as it is because he's mainly telling obese people something they've long wanted to hear:  obesity is not caused by overeating or sedentary behavior, it's not your fault.  It's hormonal, not about calories in and calories out.  Let's run ... wait ... erm ... better rephrase.  Let's slowly lift that heavy idea to exhaustion, shall we?

I'm going to stipulate to what I believe to be the underlying sentiment of the anti-ELMMers:  Fat mass accumulation is controlled by hormones.  Intake and expenditure are directed by hormones and cause you to over/undereat or be more or less active.   Adipose tissue is not just a bank where we deposit and withdraw fat, it's an endocrine organ.  And yet, among the dozens of hormones involved in the regulation of fat tissue mass (per Astwood cited in WWGF), we're to accept that insulin, and essentially solely insulin is responsible for fat cells going rogue and accumulating fat.  Not only that, only the insulin secreted in response to carbohydrate ingestion has this power ... not the insulin secreted in response to protein ingestion or fat-stimulated incretin (e.g. GLP-1)  ... that insulin is somehow different.   Ironically, in the last case other hormones, specifically glucagon, are considered.  So, other hormones are only considered when it's convenient.  Now, even if we accept this to be true ...

We are to accept that adipose tissue -- indisputably an endocrine organ in its own right secreting at more than a half dozen adipokines/hormones (leptin, ASP, adiponectin, TNF, IL-6, adipsin, resistin ...) -- is at the passive behest of your pancreas for its own regulation.  Does this make one iota of sense to anybody? I suppose the fat tissue just wants to feel important and confuse obesity researchers by secreting such a wide array of peptides, eh?  We have this intricate homeostatic sensing system to regulate fat tissue mass and ... ultimately ... the fat tissue itself has essentially nothing to do with it?  Really???!!!   And dang that Jack in the Beanstalk pancreas telling your Adipose Giant what it's supposed to do.  

Thanks to Kurt Harris for providing this citation in the comments here:  Update on Adipocyte Hormones Regulation of Energy Balance and Carbohydrate/Lipid Metabolism (2004).  This was a jumping off point, but is only the tip of the iceberg of what I had learned previously and came across in the wake of these discussions.    I had some other things in the works that I'm pushing aside for this issue.  It is that important.   But in the meantime, that paper is an excellent read.

Does everyone need to know all of the workings for some plan that is working?  Certainly not.  But misinformation is always dangerous -- at some point to some degree.   That a few escape virtually unscathed by dogmatic adherence to ideas, does not mitigate the potential harm to many others.  The time has come to put the TWICHOO back in its rightful place on the trash heap of failed hypotheses.

To be continued ...

For Part II, click here.


Diana said…
I found this interesting:

"Neither insulin sensitivity nor insulin secretion predicts spontaneous weight gain. Individuals who have attained a higher weight are prone to either gaining or losing weight regardless of their glucose tolerance."

Guess it must be somethin' else, then?
Kindke said…
"fat-stimulated incretin (e.g. GLP-1) "

What did you mean here CarbSane? and in the context of your sentence you said it in?