Why Insulin Levels & Lipolysis Do NOT Dictate Weight Loss ~ Part I

I'm really rather amazed that at this point we're still having to discuss this topic.  As a good friend of mine once said to me in an email (paraphrasing):  One would expect these sorts of myths to persist back in the 80's and 90's.  But in this day and age of information availability on the internet, it seems impossible that enough people continue to be influenced by such easily debunked notions.  Low carb Wiener anyone? {grin}

In any case, it seems that no amount of demonstrating the lack of any correlation between fasting insulin levels and weight loss will convince some people.  I really would think that the scatterplot (weight loss v. fasting insulin), discussed in this post,  would be impossible to explain away, and yet many just dismissed it from their minds.  It's that proverbial black swan all the Eades Popperites (or is that all you can eat (Eade)sous vide popper-bites?) constantly seek.  

I was yet again reminded of that paper that got me thinking and started all the fuss.  Yes, I'm talking about the infamous (around these parts anyway) 2003 Reshef et.al. paper Glyceroneogenesis and the Triglyceride/Fatty Acid Cycle that is cited as a reference in GCBC.  This is telling.  Some seven months after I first reported on this fact to my readers (to a whopping roughly 200-300 "page hits" at the time), Gary Taubes finally addressed Reshef by dismissing it as mostly rat studies.  But my interview with Jimmy apparently also got Gary to obtain a copy of Frayn's Metabolic Regulation (a later edition than the one referenced in GCBC) and get around to reading it.  In there he found a nice little picture about fat storage and the fatty acid cycle.

In any case, as Taubes now says, he knew all along that you could store fat w/o carb, you had to, because of the mere existence of the TAG/FFA cycle.  Below is the full "cycle" -- actually two cycles:

Now, I would be remiss if I didn't stress yet again how his G3P theory has always been a load of bunk.  Look at that picture.  See those bold solid arrows from pyruvate to G3P, and the rather more faint dashed arrows from glucose to G3P?  But right below that diagram in the article is a entitled "Measurement of the triglyceride/fatty acid cycle in vivo".  This is literally *right under* the diagram above, and is the Table I indicated in the caption.  I'm only including the first few lines relevant to this post (human adults!) 

In the fasted state, when according to theory we should be losing our weight because that's when lipolysis is high, almost half of fatty acids released by lipolysis are burnt and the rest are recycled back to triglycerides.  Interestingly systemic (liver) recycling is roughly 5X that of adipose.  The line below that labeled "burn" is for severe burn patients.  This is a rapid event due to acute injury.  Of note, the delivery rate of fatty acids from the fat tissue is increased a little over 3-fold.  Systemic recycling is reduced to roughly half as a percent (which would still increase the absolute amount of systemic recycling by over 50% -- or >1.5X fasting) while adipose uptake/recycling is increased almost 5-fold by percent -- this would correspond to absolute uptake and recycling back to triglyceride of roughly 15X more in absolute amounts of fatty acids.    In all, 64% of the excessive NEFA release is recycled in this scenario.  

We can add to this information from the table on p.4 of this study PDF.  I'll be blogging on this one at some future point, but looking at the "C" - normal controls - we see that NEFA (measured as oleic acid) concentrations and turnover rates are increased by exercise, but accompanied by an increase in proportion taken up.  

What does this tell us? 

• More fatty acids are continually released from fat cells than are actually used by the cells.  The supply of NEFA is thus in perpetual excess of needs.
• The amount of NEFA released is proportional to need thus more are released in response to activity (not included in table) or stress as in the burn scenario.
• Increased demand seems to elicit an "over-reaction" to mobilize NEFA accompanied by a corresponding "call to action" for adipose to quickly take up excesses.
• I think we can all agree that the "burn" cannot simultaneously cause increased and decreased insulin levels that would be required to produce the "burn" effect if insulin is sole regulator of fatty acid trafficking.  In the burn scenario, if insulin was dropped to release NEFA dramatically, then how to explain the roughly 15-fold concurrent increase in uptake/recycling?  
• Ditto for the exercise scenario.  Exercise is known to lower insulin and increase lipolysis, which is demonstrated in the linked study.  So NEFA are delivered in greater excess.  Even with greater utilization, proportionally more are taken back up.  
• Taken together these last two bullet points demonstrate clearly that something other than *just* insulin is controlling the TAG/FA cycle in adipose tissue.  
• A case can be made that uptake percents are dictated by how much is utilized by the cells for energy needs and how much remains in circulation.  In exercise ("fight or flight") or injury, the excess NEFA delivery is even more excessive to assure meeting needs.  And the fat tissue takes up the excesses just as rapidly to avoid spiraling lipid content in the blood.

So ... what dictates weight (fat mass) loss?  Mass balance.   The only way for fatty acid mass to get out of the body is through beta-oxidation to CO2 (or very minor losses of ketones).  If you oxidize more fatty acids than you take in, you lose fat mass.  If you take in more fatty acids than you oxidize, you gain fat mass.  

If the obese did not mobilize sufficiently excess NEFA to meet needs, you're cells would not be "starving" making you hungry ... You would probably be dead.

Fat Burning:  Lipolysis/release of NEFA = NEFA uptake/oxidation + NEFA recycling

Lipolysis is not the rate limiting step, it delivers NEFA in excess by design.  Uptake and oxidation is the rate limiting step.  That, and not lipolysis, determines weight (fat) loss or gain in conjunction with intake.