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Welcome all seeking refuge from low carb dogma!

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~ Charles Darwin (it's evolutionary baybeee!)

Saturday, September 10, 2011

CICO vs. Regulation of Fat Tissue ~ Questions for Gary Taubes

In an interview with Andreas Eenfeldt (some time in 2010, uploaded by Eenfeldt 3/15/11), Gary Taubes makes the following statement (~3 minute mark is a good place to start):
Look it's 2010 we have a disorder of excess fat accumulation, and people are saying that the actual physiological regulation of fat tissue is irrelevant. 
One point Stephan made in his retracted response to Gary's recent blog post needs to be addressed.  So I'll  do so here.   Folks have been letting Taubes get away with this for a very long time, and that is his indiscriminate use of the word "regulation".   The core principal of TWICHOO (Taubes Wrong Insulin-Carbohydrate Hypotheses of Obesity)  is that insulin is the primary regulator of fat tissue metabolism, and thus fat mass.  He's actually ratcheted that up a notch so that in his view insulin acts as virtually the sole regulator.  

I'm going to use a computerized multi-fuel furnace with a fuel tank system depicted below to make my analogies.

  
This analogy will be a simplistic one to reflect glucose (fuel A in blue) and fatty acids (fuel B in pink).  The furnace can operate on a wide range of fuel compositions but must have some minimum amount of A in the mix.  A quick explanation of the furnace:    On the upper right, we have the intake of A (blue 1) into a small holding tank.  The fuel is either directed immediately towards the outlet tube for burning (green 1) or diverted into an overflow system (blue 2).  At this point it can go to the overflow tank -- analogous to glycogen (blue 3) or to a converter (blue 4) which represents de novo lipogenesis essentially converting it to fatty acids, fuel B.  Once converted to fuel B the fuel can either be added to the more immediate use pool of B or long term storage overflow B (gray 1).  On the left hand side we have the intake of B (pink 1) into a small holding tank.  It can either be directed immediately to the outlet tube for burning (green 2) or diverted into the overflow tank (pink 2).  Note the break in this tank is intended to indicate the enormous size of this reservoir compared to the other tanks.  When the furnace is in use it derives fuel from all four tanks, including directly from the intake tanks for A & B as well as the overflow tanks for each, analogous to glycogen (green 3) and adipose tissue (green 4).  

Each arrow on the diagram represents a point at which there is a valve/pump all of which are at the direction of the central computer.  There are also fuel gauge sensors in each tank that relay this information to the computer.  In addition, there are "emergency" sensors that send priority signals if levels go below minimum  or exceed maximum levels.  Thus the computer in this furnace is what ultimately regulates the level of the Fuel B overflow tank -- the analogous tank to fat tissue accumulation.  Overfilling this tank will result in spillage of this toxic fuel, so the computer is programmed to make sure fuel is available for the furnace to burn, but not so much as to result in toxic spillage.

We can think of each of the four green arrows as flow control valves that govern the composition and source of the fuel mix.  A is burnt preferentially vs. B when in high supply, when A supply is low, more B is released and used.  It is perfectly consistent with well established science to envision a single signal mediating relative flows for green 1-4, and that this regulation can be controlled almost exclusively by sensors in the A intake tank.  Our analogy is insulin regulating fuel partitioning in response to carbohydrate intake.  Fuel A available?  Increase flow through green 1, decrease flow from green 2-4.  Waiting for the next fuel A delivery?  Increase flow though green 3 to maintain minimum A requirements, and green 2&4 to burn more B.  

Thus insulin regulates fuel partitioning, and in the most simplistic analysis, carbohydrates by stimulating insulin ultimately regulates fuel partitioning.  In our furnace analogy, we can envision that a sensor in A intake, with some feedback from other tank sensors, can do this.  

This, friends, is NOT insulin regulating fat accumulation.  In essence, the computer is programmed to increase/decrease flow at various points -- the computer is "passive" in this capacity, only regulating flow in response to whatever the sensors say.  

Now let's look at the overall furnace operation.  The furnace heats a room.  It cannot run with less than, say 20% fuel A.  The total amount of fuel used is determined by the temperature set on the thermostat, and the temperature of the environment outside the room.  Again, for simplicity, let's envision a scenario where we are trying to keep the room temperature some degrees above the outside environment.  When it's colder outside, the furnace must work more to keep temperature at a set point.  

Now remember, fuel B is very toxic.  As vast as the overflow tank is (let's call it OB), it has limits, and there's even some sort of spillage to a "fuel pan" as levels exceed maximum before the overage ultimately leaks into the surrounding room.  Since overages of intake for both fuels ultimately result in filling up OB, this is the tank that the central computer is ultimately tasked with regulating.  How would this be accomplished?  Well ... we need a way for the computer to sense the level in this tank that can ultimately control the fuel balance.  In other words, to keep (A+B)IN = (A+B)OUT over the long term.  Because the laws of thermodynamics, that tired old tautology (grin), dictate that if (A+B)IN > (A+B)OUT the OB will fill up and overflow.  By contrast, if  (A+B)IN < (A+B)OUT the furnace will run dry.  When you look at it this way two things become clear:
  • No matter what, the central computer has no ultimate control over A&B intake.  If finances are tight, you may well be forced to cut back on fuel deliveries.  The furnace can be programmed to sense this and automatically reduce fuel consumption by overriding the desired temperature on the thermostat and heating the room to a few degrees lower.  When prices are low over the summer, the computer can't keep you from trying to fill the tanks past capacity, though it can try to deal with your stupidity by heating the room up to a few degrees higher than what you've set on the thermostat.
  • The OB level is not "regulated" by the intake of "A".  It can't be in practical terms.  
What would ultimately regulate the OB level?  Hmmmm .... Well, we would need signals from OB to be sent directly to the central computer that controls all the valves and workings of all those arrows so that the computer could, via programming, alter various parameters so as to increase or decrease the OB level.  In other words, *regulate* it.  In this capacity the computer is taking an "active" role.  The computer is doing more than just flipping switches inside, it is acting to alter the furnace's relationship with the environment.  Either by plugging the intake ports entirely and/or increasing the fuel needs/expenditure.  

If only we had an analogy in living humans that would sense the levels of fat mass (OB) and tell our brains (central computer) to set various events in motion to keep the fat mass within certain limits.   Ahhh, but we do.  It's called leptin.   Adipose tissue is not a passive depot for fat, it is, as we all acknowledge, an endocrine organ of its own.  Fat cells secrete leptin, signalling our brains as to the levels of fat in storage.  Leptin does two things (there are probably more, but these two are the most relevant to the analogy and weight regulation).
  • Suppresses appetite:  Filled fat cells try to tell you to eat less, your body has enough.  For the furnace, the OB sensor would trigger a switch in the input valve that would refuse intake.
  • Increases energy expenditure:  Leptin dials up REE/RMR/BMR in an effort to increase caloric expenditure to prevent fat storage from exceeding capacity.  For the furnace, the OB max line sensor signals the computer to increase the thermostat setting.
So ... yes ... fat tissue does regulate its mass (or level of accumulation).  It does it via leptin.  Leptin acts on the hypothalamus.  When leptin signaling is working properly, it tells you to eat less and it burns off minor excesses.  All in an attempt to keep CI = CO and fat mass in balance.  But as with all homeostatic mechanisms there are limits.  We either lose our sensitivity to the signals, ignore them, or override them.  A discussion way too complicated to discuss here and probably where I differ most with the more academic theories on obesity.   (In a nutshell, I think we humans override this way too easily)

But what of the hyperinsulinemia associated with obesity?  It could be represented by some sort of pressure valve on that OB.  The last ditch compensatory action of the central computer is to try to contain the excess fuel in the OB. It just so happens that insulin is the hormone that can do this, and so there are sensors in that spillage  "fuel pan" that send a signal to try to prevent the spillage despite the tank being full.  These are all the same actions that control the valves to begin with.  Shut down pink 2 and green 4, but the pressure causes leakage nonetheless.

There's also another hormone fat tissue generates:  acylation stimulating protein, ASP.  Were it not for the fact that this protein acts locally on the tissue that secretes it, it would be classed a hormone.  It does much the same thing to adipocytes as insulin:  e.g. enhances glucose transport into the adipocyte and stimulates esterification of fatty acids into triglycerides.  Indeed it's effect on fat deposition seem to dwarf those of insulin.  ASP is to intake fuel tank B of the furnace what insulin is to intake fuel tank A.  It does not regulate the levels of B, but it does essentially control the pink 2 arrow.  However since it is produced by adipocytes in response to dietary fat (chylomicrons) to facilitate the uptake of fatty acids by the fat tissue itself, ASP is more integral to fat tissue than insulin from the point of view of the "lipophilia" hypothesis -- that being the notion that the fat cells go rogue hoarding fuel.

Bottom line, CICO does not regulate fat mass, but fat mass does increase when intake exceeds expenditure.  But neither does insulin regulate fat mass.  Rather insulin mediates fuel usage for that which we've taken in to meet expenditure needs.  ASP seems mostly to be responsible for keeping fat out of circulation when it presents itself in quantities requiring clearance from circulation.  Ultimately it is leptin that is produced in quantities directly correlated with fat mass.  Leptin is the regulating hormone that signals the hypothalamus, the regulator.   The hypothalamus then signals the body to up/down regulate things any number of things (including insulin secretion) so as to increase/decrease accumulation.  Leptin is how fat tissue *tries* to regulate its mass.   How leptin signalling goes awry is also a subject for another time.

So Mr. Taubes.  Here are my questions, with a little redundancy for effect.  We are now in the latter third of 2011 discussing obesity and the physiology of the regulation of fat tissue.  
How, sir, can your hypothesis and discussion the regulation of fat tissue, not include those hormones secreted by the fat tissue itself?  
How can you continue to ignore leptin and ASP? 
How can any hypothesis on the regulation of fat accumulation not include ASP and leptin? 
Tick tick tick...

33 comments:

Diana said...

Evelyn,

I had meant to ask you something about the myth of starving cells but it got lost in the fray. So it's not entirely off-topic for me to ask you here.

When Eades says, "Fat can’t get out of the fat cells, and the tissues begin to starve. Even though there is plenty of stored fat, the body can’t get to it because elevated insulin is preventing its release."

I just don't understand how someone could say this. Does he mean that an obese person's brain tissues are routinely deprived to glucose due to elevated insulin levels? Or that they can't develop muscle tissue? There are plenty of obese muscular people (tackles in football, sumo wrestlers).

Getting back to the post, if fat tissue secretes hormones, does muscle tissue secret hormones? If not, what is so special about fat tissue that it secretes hormones making it "an endocrine organ of its own"?

Lerner said...

Diana said, "Getting back to the post, if fat tissue secretes hormones..."

Fat tissue predates actual glands. Humans are more like earthworms than we care to admit.

Beth@WeightMaven said...

If you haven't listened to it, be sure to check out Robb Wolf's podcast with Taubes from this past May: http://robbwolf.com/2011/05/03/the-paleo-solution-episode-78/.

Taubes admits that he can't keep up with the literature since GCBC because he's got young kids ... but he's still insistent that it's all in the body, not the brain.

It's a bit of an odd combination to be both arrogant AND not up to speed with the literature in your field!

Sue said...

If Taubes can't keep up with latest research on obesity then he is no longer required. He did a great job bringing carbs and insulin to our attention but research has moved on. He either keeps up or he is no longer useful in up-to-date discussions on obesity. He should start writing about another subject and leave obesity to others.

Steve said...

Good stuff, CS.

I had a quesiton on this line:

"Leptin is how fat tissue *tries* to regulate its mass."

Given that liposuction doesn't result in a permanent reduction in fat loss (fat is regained), there must be something else other than leptin regulating fat tissue, right?

Kindke said...

"We either lose our sensitivity to the signals, ignore them, or override them. A discussion way too complicated to discuss here and probably where I differ most with the more academic theories on obesity."

"How leptin signalling goes awry is also a subject for another time."

CarbSane, you could make your next post about this stuff, but I guess its easier to mock and poke fun at other people isnt it?

Kindke said...

Steve fat mass regulation is much more complicated than just leptin.

Having said that though I think funnily enough leptin probably does fully account for weight regain following liposuction, if you suddenly remove a load of fat cells your almost surely going to be leptin insufficient, and leptin insufficieny is a extremely powerful driver of fat gain.

Kindke said...

"but fat mass does increase when intake exceeds expenditure."

That is stating the obvious. Your talking about the effect of obesity, not the cause, just as Taubes says.

If I inject myself with androgen receptor agonists, my calorie instake will increase and I will gain loads of muscle mass. The increased calorie intake surely does help drive the increased muscle mass, but it didnt CAUSE it. The increased calorie intake is the effect of the increased anabolic signalling. Hormonal signalling gets the ball rolling, not gluttony.

This is what happens in obesity, hormonal signalling starts the ball rolling, but apparently obesity researchers have a hard time comprehending that.

Evelyn aka CarbSane said...

@Diana: Maybe we are more like worms as Lerner says! LOL. I don't know why it would be that fat tissue behaves like an organ except that the fat tissue fatty acid cycling is critical to ensure we always have fatty acids to burn (just as the liver is charged with ensuring we always have glucose) and for maintaining body temp. In rodents, thermogenic brown fat plays a larger role in this -- this is probably due to the larger surface area/volume ratio of smaller animals.

@Steve: Thanks! I think Kindke answered your question in one way that makes sense, remove some leptin production, eat a little more to restore it. Another explanation could also be that we are creatures of habit. The person who "loses" 5lbs without changing their habits will gain it back until again CI=CO.

@Kindke: Thanks for your advice on how I should write in my blog. It's funny, really. When I write about how I believe most of us get/got fat, I get ridiculed. IMO the obesity epidemic will not be explained by biochemistry and endocrinology. Humans eat for reasons other than hunger, and our daily lives are hardly those of "wild" animals.

Evelyn aka CarbSane said...

@Kindke: Y'know there are bloggers who will scream the next time they hear Kitivan. I'm going to scream the next time I hear tautology or any version of that.

As to your muscle growth example, did this whole post go over your head? Did I say hormones have nothing to do with partitioning? Hormones play a huge role in that. It's why women are fattiER than men in general. But you said a key thing in your example: injection. But you're still deliberately eating more.

Evelyn aka CarbSane said...

@Beth: Sigh. I agree with Sue. If Taubes can't keep up he shouldn't be "active". Funny how WWGF was touted as containing new evidence. Actually he just left out the parts too many people know he's wrong about. I don't recall which interview, but this "I have two small children and no time" thing is repeated often. He once said that he must be right because nothing new has come along showing him wrong. I get frustrated by the fact that one doesn't need new, they just need research done since the advent of newer methods to assess various things.

Kindke said...

I have a crazy theory, CarbSane you say that insulin is in a negative feedback loop with plasma FFA to maintain it within tight ranges.

In the same way, I think leptin is in a negative feedback loop with energy intake and energy expenditure. ( through adipocyte volume )

Insulin acts on adipocytes, leptin acts on the central nervous system and AgRP neurons in the hypothalamus.

Some recent studies have shown that the proportion of AgRP neurons in the hypothalamus changes during calorie restriction. In the same way that more insulin is needed keep large fat cells spilling FFA, my guess is that more leptin is needed in the hypothalamus to keep the increased amount AgRP neurons in check. This is "relative" leptin insufficieny.

Ofcourse leptin will also drop off with fat cell volume.

blah this sounds like what lyle mcdonald talks about in his bromocriptine book.

fat cell hyperplasia is a big reason why people get fat, the newly born fat cells are tiny and incredibly insulin sensitive, this means that esterification of trigs proceeds at an accelerated rate compared to the mature adipocytes in the nearby neighbourhood for a given insulin concentration.

Rapid esterification occurs until the new adipocyte reaches the approximate size of neighbouring adipocytes, lipolysis and esterification will then be in balance with the local insulin concentration, preserving the feedback loop.

This should happen independent of the persons CICO, all we need is the stimulus for fat cells to divide.

Evelyn aka CarbSane said...

Kindke -- where do the fatty acids come from to be esterified in all of these fat cells? Excess in the diet (most fat in the cells came ultimately from fatty acids in the diet). Gary Taubes seems to be highlighting the "lipophilia" concept more these days (it's all he's got left). But there's no support for this except in rare genetic instances (it may have been you even who posted here about the girl who was obese but didn't overeat?). The thing is, the pre WWII Austrian/German research was about those rare cases. This notion that eating carbs causes fat cells to "go wild" is not supported by any evidence I've seen.

Kurt G. Harris MD said...

Very nice model here for fuel partitioning.

I've used a similar but cruder verbal metaphor of a multi-fuel stove for some time, thinking of the MSR backpacking stoves that run on white gas or diesel. A metabolism designed to run on what is available, but not not both at the same time...

The confusion between necessary and regulating I find, well, confusing.

It shouldn't be confusing to think that insulin is required for fat storage but is not the primary regulator of same, any more than understanding that your car engine and a full tank are necessary for forward progress, but the throttle assembly and fuel delivery system regulate your speed.

"ASP. Were it not for the fact that this protein acts locally on the tissue that secretes it, it would be classed a hormone."

ASP is legitimately a hormone. Its primary action on the cell elaborating it is an autocrine (self-acting) hormone function, but there is evidence for endocrine function effected by plasma levels of ASP as well.

http://diabetes.diabetesjournals.org/content/53/suppl_1/S143.full

Evelyn aka CarbSane said...

WOW Kurt! This is an amazing paper. It will take some time to digest all of the refs. within. But a heart felt Thank You for it.

Sue said...

Yeh, great paper. I'm giving it a read now. Have you seen Peter at Hyperlipid latest (a defect of fat metabolism ...)- some interesting comments. Evelyn, would like your take on it.

Evelyn aka CarbSane said...

Hi Sue, I've got parts II & III in the works for one of the gnolls cites on impaired oxidation. I'm going to look at a few of Woo's references but her writings are a rough slog. I think she's probably one of those rare genetically obese. What pertains to her case probably doesn't pertain to those who are part of the "epidemic". Mitochondrial dysfunction is likely due to sedentary behavior in the face of nutrient excess.

Qw said...

What's the calorie theory?

Tsimblist said...

"Mitochondrial dysfunction is likely due to sedentary behavior in the face of nutrient excess."

I suspect that sedentary behavior is sufficient for dysfunction and that nutrient excess aggravates/accelerates the problem.

Sue said...

Thanks Evelyn.

Kurt G. Harris MD said...

@Evelyn

You are welcome.

Fred Hahn said...
This comment has been removed by the author.
Fred Hahn said...

Hi Evelyn -

You said:

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

Leptin resistance isn't an issue until you are already fat. To get fat or not to get fat, that is the question.

As for ASP, here you go:

http://slowburnfitness.com/fat-regulation-insulin-or-asp/

Fire away. I have more.

Evelyn aka CarbSane said...

Welcome QW: Calorie theory is another way of saying "calories in calories out" or a version of addressing energy balance.

Fred: Leptin is produced by fat, acts on the hypothalamus and is intimately involved in the regulation of total fat mass. Insulin resistance isn't an issue in the obese who are IR until they are already fat, so are you saying insulin is not important?

You erected strawmen (per usual) in your blog post and question to Keith Frayn. I don't have the time to debate in circles with you, especially when I'd have to spend time tearing down the strawmen first.

It seems you missed the point of this blog post. It's about what regulation really means.

Fred Hahn said...

"Fred: Leptin is produced by fat, acts on the hypothalamus and is intimately involved in the regulation of total fat mass."

Yes I know. But you won't have a leptin problem if you're not fat - it would be very unusual at least. Too much fat can = too much leptin which can result in leptin resistance. But We still need to know why we got fat in the first place.

"Insulin resistance isn't an issue in the obese who are IR until they are already fat, so are you saying insulin is not important?"

I don't understand your question. Could you rephrase that?

"You erected strawmen (per usual) in your blog post and question to Keith Frayn. I don't have the time to debate in circles with you, especially when I'd have to spend time tearing down the strawmen first."

Not to be rude but it seems that you don't know what a strawman argument is. I encouraged my readers to read your entire post before continuing with mine so that they could completely understand your position. I quoted you word for word.

Tell us all now then - do you disagree that insulin is the main fat regulating hormone?

"It seems you missed the point of this blog post. It's about what regulation really means."

Yes I got that. Again, do you disagree with Dr. Frayn that insulin is the main regulator of fat? It sure isn't ASP as you claim it is. Oh wait - did I build a strawman again?

Here is what Dr. Frayn said:

"Hi Fred

My guess is that you are right: insulin is the primary regulator of both fatty acid uptake and fatty acid release. The ASP story was a nice one but I don’t think it’s been substantiated.

Best wishes

Keith"

So do you have information that supercedes Dr. Frayn's statement? Some science he doesn't know about? Some facts he's missed?

If so, I would certainly be interested in reading whatever it is you have. So would a lot of people I know.

Evelyn aka CarbSane said...

Yes I do. You set up two big ones in mischaracterizing what I said.

Insulin isn't a problem unless you're fat either. For the majority anyway. And those "skinny fat" folks tend to have leptin issues as well. So your leptin argument falls short.

Actually there is some evidence not from a Frayn-related research group that directly implicates ASP action in overall energy homeostasis.

Again, do you disagree with Dr. Frayn that insulin is the main regulator of fat? It sure isn't ASP as you claim it is. Oh wait - did I build a strawman again?

Yes. This is not what I've ever said.

Fred Hahn said...

"Yes I do. You set up two big ones in mischaracterizing what I said."

You are STILL evading the issue. And STILL ignoring the fact that I told my readers to read your blog in its entirety before continuing to read my blog post. I suggested this so that people would have a complete understanding of your position. How many more times will you ignore this?

"Insulin isn't a problem unless you're fat either. For the majority anyway. And those "skinny fat" folks tend to have leptin issues as well. So your leptin argument falls short."

I said that for the most part if you are lean, you won't have leptin resistance issues. Some do and for those who are lean and have leptin resistance, they need to deal with that. But they are not obese and we are talking about those who are obese and how they got that way so it's beside the point.

Insulin is insulin. No one is saying that insulin is bad or a problem or a monster to be slayed. But it is the primary regulator, as far as we know, of fat.

"Actually there is some evidence not from a Frayn-related research group that directly implicates ASP action in overall energy homeostasis."

And where is this info?

I said: "Again, do you disagree with Dr. Frayn that insulin is the main regulator of fat? It sure isn't ASP as you claim it is. Oh wait - did I build a strawman again?"

"Yes. This is not what I've ever said."

Then what do you mean by this:

"ASP is a potent agent in triglyceride clearance from circulation, insulin less so, although it can stimulate ASP. But this study did demonstrate that IF we are to point to fat accumulation, ASP is the big Kahuna. Insulin is not, as far as I know, directly involved in fatty acid uptake (as in transporting it).”

Evelyn aka CarbSane said...

Fred, do not confuse not wanting to engage someone who is notorious for circular unsubstantiated arguments with evasion.

I never said ASP was the primary regulator of all fat metabolism. That's your strawman. In terms of triglyceride uptake, ASP does seem to play the major role according to the studies (Frayn & others). Fatty acid uptake = transport into cells, clearance from plasma. Chylomicrons stimulate ASP to facilitate the rapid uptake and clearance of dietary triglycerides. Insulin levels are low even after a mixed meal when fatty acid uptake is highest.

Most skinny people have no problem with insulin, and the basal hyperinsulinemia is the result of becoming obese not the cause. That's been blogged on here, I suggest searching my blog for "fasting insulin". So if your position is that leptin is irrelevant until we get fat, my response is that so is insulin.

You cannot discuss the WHOLE PICTURE of fat tissue metabolism/accumulation/energy homeostasis w/o including leptin and ASP. I stand by that. Taubes and his true believers would prefer we not look at the whole picture to promulgate a failed hypothesis of why we get fat.

I've not yet blogged on some of the newer ASP info. You'll have to read the blog. I do have feeds enabled.

Discussions with you have, in the past, been unproductive. So why bother? If you want to share your vast knowledge with my readers feel free to comment, but don't expect a response. I'd rather spend the time I have blogging or interacting with those who are interested in productive discussions, even from opposing viewpoints.

Fred Hahn said...

"Fred, do not confuse not wanting to engage someone who is notorious for circular unsubstantiated arguments with evasion. I never said ASP was the primary regulator of all fat metabolism. That's your strawman."


Here's what you said:

“ASP is a potent agent in triglyceride clearance from circulation, insulin less so, although it can stimulate ASP. But this study did demonstrate that IF we are to point to fat accumulation, ASP is the big Kahuna. Insulin is not, as far as I know, directly involved in fatty acid uptake (as in transporting it).”

What do you mean exactly then?

"In terms of triglyceride uptake, ASP does seem to play the major role according to the studies (Frayn & others)."

Let me repeat Frayn's words:


"The ASP story is very controversial. A number of people have not been able to reproduce the claimed effects of ASP. So I think we’re still in the dark. But insulin definitely does work! I can’t say for certain but my bet is that insulin is the major regulator of this step, with maybe some local ‘fine-tuning’ by ASP."

"Fatty acid uptake = transport into cells, clearance from plasma."


But not necessarily into the fat cells themselves.

"Chylomicrons stimulate ASP to facilitate the rapid uptake and clearance of dietary triglycerides. Insulin levels are low even after a mixed meal when fatty acid uptake is highest."

You are completely misunderstanding the conclusions.

"Most skinny people have no problem with insulin, and the basal hyperinsulinemia is the result of becoming obese not the cause."

Wrong.

"That's been blogged on here, I suggest searching my blog for "fasting insulin". So if your position is that leptin is irrelevant until we get fat, my response is that so is insulin."

Not according to Frayn.

"You cannot discuss the WHOLE PICTURE of fat tissue metabolism/accumulation/energy homeostasis w/o including leptin and ASP."

Fine tuning at best as Frayn said.

"I stand by that. Taubes and his true believers would prefer we not look at the whole picture to promulgate a failed hypothesis of why we get fat."

Talk about strawman arguments!!!!

"I've not yet blogged on some of the newer ASP info. You'll have to read the blog. I do have feeds enabled."

I'll be there.

"Discussions with you have, in the past, been unproductive. So why bother?"

You seem to be bothering so what's your point?

"If you want to share your vast knowledge with my readers feel free to comment, but don't expect a response."

I don't have vast knowledge of anything. And your statement is rather snarky.

"I'd rather spend the time I have blogging or interacting with those who are interested in productive discussions, even from opposing viewpoints."

Productive discussion? I just shared with you and everyone who reads my blog (and yours) the thoughts and opinions of one of the world's leading experts in fat metabolism. How more interested must I prove to be?

You should be intrigued and incredibly interested in what Dr. Frayn has to say on this issue. Instead, you are snarky, dismissive and accusatory. If anyone is not interested in a productive discussion it is you.

It's funny, you are lightening quick to attack people viciously and venomously for what you perceive to be errors in their work and character, but then act impervious to evidence - even conclusive evidence - that you yourself have made copious errors.

Telling indeed.

Fred Hahn said...

You said above:

"In terms of triglyceride uptake, ASP does seem to play the major role according to the studies (Frayn & others)."

This has nothing to do with becoming obese.

Evelyn aka CarbSane said...

Fred: See my latest post.

So uptake of dietary fatty acids into fat tissue doesn't have anything to do with making youobese, but re-uptake of fatty acids from circulating NEFA and VLDL triglycerides does. Uh huh.

Fred Hahn said...

"So uptake of dietary fatty acids into fat tissue doesn't have anything to do with making you obese,..."

It can and this is best accomplished by eating a large amount of refined / high GI carbohydrates which causes large secretions of insulin resulting in IR over time.

"...but re-uptake of fatty acids from circulating NEFA and VLDL triglycerides does. Uh huh."

Ooo...you made a very nice strawoman argument. Nicely done!

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