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Fat Regulation: Insulin or ASP?

by Fred Hahn on September 10, 2011

insulin_influence

When we eat and get fatter, how does that work exactly? What mechanisms are at play that turn the things we eat into the goo that gets stuffed into our fat cells?

Fat inside a fat cell called a lipocyte
Fat inside a fat cell called a lipocyte

Many nutritional experts say obesity is caused by eating and drinking too much – taking in too many calories in other words. Well, OK, but when we do overindulge, how does the excess turn into fat? Why doesn’t it turn into muscle, bone or organ tissue?

Insulin or ASP
There’s been some debate about the role of ASP in the regulation and storage of fat tissue. Some argue that Acylation Stimulating Protein (ASP) is the main regulatory lipid hormone and not insulin. Based on a series of papers and this one from late 1998, some have taken these papers to mean that ASP plays not only a critical role in fat storage and retention, but the critical role.

If it is ASP, this means significant amounts of body fat can be gained and retained merely by eating fat; that carbohydrates are unnecessary to stimulate insulin secretion, because ASP will do the fat storing and imprisoning job all by its lonesome.

But is it? Is it ASP or insulin that is the “boss” of fat?

This is what the current edition of Lehninger Principles Of Biochemistry says about fat storage in adipocytes:

“High blood glucose elicits the release of insulin, which speeds the uptake of glucose by tissues and favors the storage of fuels as glycogen and triaglycerols, while inhibiting fatty acid mobilization in adipose tissue.”

Seems like an open and shut case for insulin being the boss of fat regulation. But perhaps there’s more to it than this.

To find out more, I figured I’d do the obvious and actually ask the man who wrote the series of papers I mentioned earlier. His name is Dr. Keith Frayn. Dr. Frayn is from Oxford University and is considered one of the world’s leading experts on fat metabolism. If anyone knows anything about what regulates fat in the human body, it’s him.

But before I tell you what Dr. Frayn said, here are a couple of snippets about ASP written by a blogger known as Carbsane. She is one of several bloggers who believe that the carbohydrate/insulin hypothesis of obesity is bogus, meaning, not the primary cause and that those who support it are misinforming the gen pop:

“ASP is mentioned in Frayn’s latest version of Metabolic Regulation, but unfortunately texts are woefully outdated. They are NEVER considered better references than peer review journal articles. Read my latest blog on a Frayn article: Factors stimulating tissue retention of fatty acids include insulin and acylation stimulating protein. ASP is a more potent stimulus to fatty acid uptake and esterification in adipocytes than is insulin.”

“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).”

Really? Insulin is not directly involved in fatty acid uptake?

What’s interesting about this statement is that in Dr. Frayn’s 2010 textbook Metabolic Regulation (3rd edition) there’s still very little mention of ASP and the section on fat accumulation says nothing about it.

Carbsane has suggested in her blogs that Gary Taubes, author of Good Calories, Bad Calories and Why We Get Fat has committed intellectual dishonesty by stating that insulin is the main fat-regulating hormone and not ASP.

“I am increasingly convinced that Taubes deliberately maintains a state ignorance on such matters as ASP.  Because it pretty much demolishes his hypothesis.”

She says this because she thinks (stated in her blogs) that Taubes and others who support the insulin/obesity hypothesis purposefully ignore the work done by Dr. Frayn (and others) on ASP subsequent to the printing of his 1998 text book. You can read her statement here in the body of the blog and in the comments section . In fact, if you are really interested in this issue, please read her blog post before continuing with this one. If I’ve got it wrong, reading her blog will set the issue straight. You be the judge.

If Carbsane (and others) are right in thinking that Dr. Frayn believes ASP is the main fat regulating hormone and not insulin, it seems really odd that Dr. Frayn would choose to exclude this information in his 2010 textbook. Why would he omit such a discovery? You’d think that such a fact would have Dr. Frayn penning much about it.

Let’s see if she (and others) are right about insulin not being the main fat regulating hormone. Let’s see if ASP is really the “big kahuna,” as Carbsane puts it, of fat regulation and find out the reason why Dr. Frayn made so little mention of ASP in the new edition of his textbook.

As I mentioned earlier, contacting Dr. Frayn seemed like the obvious thing to do. Here is the word for word email exchange that resulted. It’s true that our conversation is a half year old now, but I’ve been busy and the points are clear.

From: Fred Hahn [fhahn@seriousstrength.com]
Sent: 11 February 2011 18:49
To: Keith Frayn; [mailto:keith.frayn@oxlip.ox.ac.uk]
Subject: A question on ASP
Dear Dr. Frayn,

I was wondering if you could answer a question for me on insulin and acylation-stimulating protein (ASP).

Of the two, which is a more potent stimulator of fatty acid uptake? A biochemist said that it is not controversial; that ASP is a more potent stimulator of FA uptake/esterification than insulin. I gleaned from your textbook that insulin was by far the main regulating hormone of fat storage and release and at best ASP was secondary. Am I correct? Any clarification is greatly appreciated.

Thank you very much for your time.

Sincerely,
Fred

His response:

From: Keith Frayn [mailto:keith.frayn@oxlip.ox.ac.uk]
Sent: Saturday, February 12, 2011 3:47 AM
To: Fred Hahn
Subject: RE: A question on ASP

Hi Fred

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.

Hope that helps. Have you seen edition 3 of my textbook? Out in 2010. (http://eu.wiley.com/WileyCDA/WileyTitle/productCd-1405183594.html?productCd=1405183594 )

Best,

Keith

I wanted Dr. Frayn to be a bit more specific. So I sent him another email. He replied promptly.

From: Fred Hahn [mailto:fhahn@seriousstrength.com]
Sent: 12 February 2011 20:56
To: Keith Frayn
Subject: RE: A question on ASP

Thank you Dr. Frayn.

A blogger I recently read (she is a research scientist) who quotes your textbook often, quoted your article on ASP (which confused me given what your response was to my question):

“Factors stimulating tissue retention of fatty acids include insulin and acylation stimulating protein (ASP) and ASP is a more potent stimulus to fatty acid uptake and esterification in adipocytes than is insulin.”

She goes on to say:

“ASP is mentioned in Frayn’s latest version of MR, but unfortunately texts are woefully outdated. They are NEVER considered better references than peer review journal articles. Read my latest blog on a Frayn article:

http://carbsanity.blogspot.com/2011/02/non-esteried-fatty-acid-metabolism-and.html

Here she is referring to your 1998 version. I assume that ASP is not mentioned in the 2010 version of your textbook as the main fat regulator (I know this because a friend has it and he looked) over insulin because, as you said, no one has been able to replicate ASP as the predominant fat regulating hormone?

I don’t want to take up too much of your time Dr. Frayn, but I and several other people are very interested in this subject and wonder if elevated insulin (and to a lesser extent ASP) levels are what is responsible for excessive fat accumulation in adipocytes.

I think we can definitely state that insulin’s the regulator of fatty acid release through its action on HSL. That’s enough evidence, wouldn’t you say, for it to be the primary regulator of fat accumulation? I say this because if insulin keeps fat in the fat tissue, it’s not all that important whether insulin or something else puts it there though I think high insulin levels caused by high carbohydrate intake sure seem to facilitate greater fat accumulation especially in the presence of high fat which is how most people eat.

So, I guess the bottom line question is, given what we currently know about insulin, is insulin the primary regulator of fatty acid uptake as well as the primary regulator fatty acid release, not ASP?

Thank you,
Fred

His response:

From: Keith Frayn [mailto:keith.frayn@oxlip.ox.ac.uk]

Sent: Monday, February 14, 2011 2:45 AM
To: Fred Hahn
Subject: RE: A question on ASP

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

There you have it. ‘Nuff said.

I've been involved in exercise ever since I became a member of The Charles Atlas Club when I was 10 years old. In 1998, I founded and established Serious Strength on the Upper West Side of NYC. My clients include kids, seniors (and everyone in between), top CEOs, celebrities, bestselling authors, journalists and TV personalities.
my book. my Gym.

in diabetes,Health/Fitness,Nutrition,obesity · 36 comments

{ 36 comments }

gharkness September 11, 2011 at 8:23 PM

Very interesting story, Fred. The only thing is: I hate to see this person – who I will not name (even though you did) – gain the credibility of being part of a serious discussion. I have read this person’s blog and, while I have absolutely zero problem with people who disagree and wish to argue the FACTS, no one with such a dysfunctional attitude, who calls names (very ugly accusations!) and makes snide remarks, should even be recognized as a serious participant in the discussion.

Well, anyway, I am glad to hear of the answer you got from Dr. Frayn.

Ramona Graham September 12, 2011 at 12:47 AM

Fred! NICE!

and thank you,

your faithful reader and student,

Ramona

Heather Flannery September 12, 2011 at 7:01 AM

Hi Fred,

I just came across this through a Facebook post from “Amy’s Primal Hale.” I’m so pleased I did. I commend the clear-thinking and determination you applied to this problem, and your strategy of going to the source and remaining at all times, “on the high road.” Please keep up the great work. I’ll now be following you, and if I identify an opportunity to collaborate you’ll be on my short list.

Best regards,

Heather Tollerson Flannery | CEO
Obesity Prevention, Policy & Management, LLC
ObesityPPM.com | Twitter.com/ObesityPPM
Facebook.com/ObesityPPMLLC

Fred Hahn September 12, 2011 at 9:08 AM

Hi Heather. Thanks for the kind words! I’d be happy to collaborate!

Fred Hahn September 12, 2011 at 9:37 AM

Thanks Ramona. I hope this blog post gets around the blog sphere specifically to those who question the carbs/insulin/obesity/diabetes hypothesis.

Shannon September 12, 2011 at 12:08 PM

What a great post! I’m so glad I found you! I just love all these opinions whether they agree or disagree, it’s fun just to learn. I loved Gary Taubes book “Why We Get Fat,” but had a hard time believing it the first time I read it. It wasn’t until I read it again and tried his principles on myself did I become a believer in insulin’s relationship with fat metabolism. I accomplished my weight loss in just a few weeks by lowering my carbohydrate intake and increasing fats. Interesting! I still love a good debate, however, so thank you for this article, Fred!

Fred Hahn September 12, 2011 at 2:14 PM

You’re welcome Shannon!

Jami Good September 13, 2011 at 5:36 PM

Thank you for this post, Fred. I was aware of some of the kerfuffle between some members of the Paleo/Primal/Low Carb and even High Carbers, lately, but I didn’t understand what all the fuss was about. This has cleared up some of the confusion for me…now to learn more about Food Reward Theory! 🙂 If anything, the controversy has propelled me toward gaining more knowledge for myself!

Fred Hahn September 13, 2011 at 6:07 PM

The FRT is complete nonsense. So what that you eat the foods you like? I feel rewarded by homemade stock and fatty steaks, and wild caught trout. I don’t see people who feel rewarded by these foods getting fat. It doesn’t explain why we get fat at all! So what that you eat a lot of food – WHY does that food turn to fat???

CarbSane September 14, 2011 at 9:39 PM

So many strawmen, so little time.

Fred Hahn September 14, 2011 at 9:50 PM

Evelyn –

I encouraged people to read your blog in its entirety. People are smart. They will make their own conclusions.

Your ASP position is a dead end street. Move on.

CarbSane September 16, 2011 at 1:40 PM

Fred: Please cite me with attribution — e.g. a link to the post to which you are referring. Thanks.

Fred Hahn September 16, 2011 at 1:45 PM

Please be more specific. What are you talking about? And I’ll address your new blog quite soon.

CarbSane September 17, 2011 at 10:09 AM

You quoted a fair amount of text from a specific blog post without a link to that post. Proper citing would include a link either directly before or after such a quotation.

Fred Hahn September 17, 2011 at 11:23 AM

Evelyn –

I’m not understanding you here. What I did was I added a line to say that people should read the comments section of your blog as well – the one I hyperliked to. I hope that helps.

Other than that, I don’t see where I did not post the original blog for anything I quoted you as saying. If so, which one was it and I’ll add it right away. My apologies if I missed something but I don’t think I did.

Evelyn, IMHO and with no disrespect intended, I feel that you’re on a crusade to justify eating your favorite carbs. I have many clients who bring me articles by Dr. Oz, Ornish, Essylstein, etc. to justify their carb addiction. You are doing this from a biochemists perspective.

The only way you are going to become lean and muscular and as healthy as possible is if you ditch grains entirely and replace the carb calories with fat. If you were my client, I’d have you at your goal in 6 months.

I mean this with all sincerity and respect.

CarbSane September 17, 2011 at 12:15 PM

Oh, I see now. When I read “my blog” or “her blog” I think the blog as a whole. Rather “this post on her blog”, etc. It would be more clear had you linked to the blog post and then put the quotation, rather than just a “here” later on.

As to me you have no clue what the frig you’re talking about. Perhaps you should use your psychoanalytical powers to turn many of your low carb friends into better representatives for the wonders of low carb.

CarbSane September 17, 2011 at 12:37 PM

By the way, “justifying an addiction” is offensive verbiage Fred. I’m not addicted to anything. Have you been spending too much time on The Bunnell Farm?

In comments on my blog you’ve accused every low carber who is not “at goal” of cheating — dishonesty or fatal character flaw. Makes no difference. I wonder what the still obese low carbers who follow the way of eating diligently think of that.

You have decided, based on no scientific evidence or epidemiological evidence that a VLC diet is the only and best diet for humans. Anyone who disagrees is just justifying things. 99.99% of humans who have ever lived were addicts and never knew it. Sigh.

I’ll be blogging on the whole picture of fat tissue mass regulation. In case anyone’s interested. Installment 1: Full Physiological Regulation of Fat Tissue ~ Part I

Fred Hahn September 17, 2011 at 1:04 PM

“Oh, I see now. When I read “my blog” or “her blog” I think the blog as a whole. Rather “this post on her blog”, etc. It would be more clear had you linked to the blog post and then put the quotation, rather than just a “here” later on.”

OK I’ll change it.

“As to me you have no clue what the frig you’re talking about. Perhaps you should use your psychoanalytical powers to turn many of your low carb friends into better representatives for the wonders of low carb.”

So very snarky! I take this to mean you are not at your goal body composition. Many of my LC friends, as you so snarkily put it, have lost hundreds of pounds collectively. They continue to struggle with their weight for the exact same reason you do – they try to justify their desire for carbs and either a. lose control here and there or b. find low carb substitutes that skyrocket blood sugar halting fat loss in its tracks.

BTW, it is you who are using too fine a microscope and missing the bigger picture WRT how and why we get fat.

We know that ASP is strictly secondary in regulation of adipose tissue. In humans, leptin too, is secondary, or at least does not play the kind of strong role that it does in rodents according to the literature – animals BTW that are designed to eat a lot of carbohydrates.

Fred Hahn September 17, 2011 at 1:45 PM

“By the way, “justifying an addiction” is offensive verbiage Fred. I’m not addicted to anything. Have you been spending too much time on The Bunnell Farm?”

Carb/sugar addiction is an established fact. It’s real IOW. It’s not offensive to say someone is addicted to nicotene or alcohol. If it is offensive to someone, that’s a clear sign they are addicted. Many of my clients admit they are addicted to sugar/carbs. It’s only offensive to say this in an intentionally offensive way which I did not.

“In comments on my blog you’ve accused every low carber who is not “at goal” of cheating — dishonesty or fatal character flaw. Makes no difference. I wonder what the still obese low carbers who follow the way of eating diligently think of that.”

Oops – another strawoman slipped in. But no matter, I think the ones who are honest (and those who are not suffering from health disorders and are on drugs like steroids that are making them fat) will take it just fine. The truth is what it is.

“You have decided, based on no scientific evidence or epidemiological evidence that a VLC diet is the only and best diet for humans. Anyone who disagrees is just justifying things. 99.99% of humans who have ever lived were addicts and never knew it. Sigh.”

Strawoman #2. You’re good at spinning these out of thin air! I have no idea where you extrapolated that statement from.

“I’ll be blogging on the whole picture of fat tissue mass regulation. In case anyone’s interested. Installment 1: Full Physiological Regulation of Fat Tissue ~ Part I”

VG! A word of advice: Make sure you show your blog to Frayn and/or Feinman before you publish it to make sure you have your facts in order. You wouldn’t want to misinform people anymore like when you said that ASP is the big kahuna of fat regulation.

palo September 17, 2011 at 3:49 PM

Hey Fred, once again carb(in)sane – a member of the evil axis that includes crackpot colpo and gayturd krieger – strikes again.

She can’t stand that Dr. Frayn’s response to you has left her literally naked. Her whole ELMM weight management theory has gone down the drain. But it was never valid anyway.

We have a saying where I’m from that “before you talk the talk, you have to walk the walk.”

Dietary directives coming from carb(in)sane are completely laughable.

By her on admission, before she came out of the closet (revealed her name), she said that she had been stalled at 200 lb. in a 5’3″ frame FOR THREE YEARS!

A look at her picture on her website shows either an obese woman or a woman with the head of an extra large frying pan! And she is an “expert” in dietary advice?

Not only is she addicted to carbs, she is addicted to malice, vitriol and a mean spirit towards humanity.

Fred Hahn September 17, 2011 at 5:28 PM

Palo, well those are some choice words there. Perhaps a bit too judgmental, no?

I agree, however, that Carbsane is addicted. According to Dr. William Davis, author of Wheat Belly, some people are so extremely carb/wheat addicted their minds and emotions actually become altered and they will confabulate stories and ideas about carbs that are completely false. I’m not saying that Evelyn is this addicted, but she could be.

In her defense, you can be obese and also right about the science behind obesity. And it’s not that everything she says is wrong of. But she is indeed trying her darnedest to prove that carbs are not the reason for why we get fat to the same degree that alcoholics try to justify that their drinking is not a problem.

I have a new client who has severe osteoporosis. She eats a lot of grain and very little fat or meat. After I explained to her that the grain consumption is contributing to her osteoporosis, she became very defensive, told me that grains are good for HER, brought me in all kinds of vegan propaganda, and flat out told me that she will not quit eating the grains. It was as if I said God is evil to a priest. She then tells me she is perfectly healthy and grains make her feel great. I then remind her that she is far from healthy – she has the shakes, is rail thin and has osteoperosis!

Addiction runs deep. I’m not a therapist but I can tell when someone is addicted by their irrational and often venomous behavior mixed with strong denial.

palo September 18, 2011 at 5:27 AM

Hey Fred, I get very upset whenever I see these charlatans bamboozling people with junk science, preventing them from becoming healthy and fit.

Fred Hahn September 18, 2011 at 8:45 AM

I understand Palo. I feel the same way. I too have fallen prey to saying things I shouldn’t have said. I ain’t no Thomas Jefferson that’s for sure! 😉 We all get heated. “Fahgettaboutit” as they say in Brooklyn!

mrfreddy September 18, 2011 at 9:56 AM

Fred, I have to disagree with you if you are saying that anyone on a low carb diet who stalls out, it’s because they are somehow someway eating too many carbs. It seems pretty evident that even on a low carb diet, a LOT of people fall short of loosing all the weight they need to. In my own case, I’ve been low carbing almost 10 years, and I know for an absolute fact that I rarely eat more than, say, 30 grams carbos per day, and most of the time far less than that. But I have been about 10- 15 pounds or so overweight almost all of this time.

If I want to lose more, the solution isn’t, hmmm, where am I getting too many carbs in my diet? It’s probably, hmm, cut the booze, maybe cut the dairy, and dare I say it, maybe even cut the calories. Or I suppose, according to the food reward folks, it’s eat boring foods.. (but who wants to do that?!)

Alex September 18, 2011 at 10:05 AM

I think all this can be summed up by referencing the phenomenon known as ‘cognitive dissonance’!

CarbSane continually references Dr Frayn in support of her contention regarding ASP vs. insulin but appears to be ‘cherry-picking’ from his work. As you have shown, Dr Frayn does not consider ASP a prime mover in fat storage:
“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.”

And even if you reference his work as far back as 2003 (Integrative Physiology of Human Adipose Tissue in the International Journal of Obesity) he and his colleagues say (in conclusion to their paragraph on ASP:
“The production of ASP in vitro is stimulated by the presence of chylomicrons and its production by adipose tissue in vivo increases in the postprandial period giving ASP a potential role in coordination of postprandial fat storage. However, physiological importance in humans remains unclear at present.”

Then they begin their next paragraph with:
“The pathway of fat mobilisation is exquisitely sensitive to suppression by insulin.”

Of course, CarbSane seems happier quoting earlier studies (1998) by Frayn, rather than later reviews where he is more cautious in his conclusions and what he said to you in correspondence just six months ago!

Brandon Schultz, D.C. September 18, 2011 at 10:41 AM

Hi Fred,
I’m amazed at how defensive people can get when you address some of their current habits (that they have come to deeply believe in from “real” experts) that their current situation – whether is it obesity, osteoporosis, etc. – is NOT caused by what they are eating or their other lifestyle choices. With my patients I just patiently (the best I can, anyway) work with them to implement small changes in the right direction.
Another addition to the “addiction” concept being spoken of is Dr. Holder’s work with a concept called “Brain Reward Cascade”, which may be closely linked to the neurotransmitter response to a high card meal/diet and why people may get “hooked” on carbs and have a hard time decreasing their intake.
http://www.torquerelease.com/art5.htm
Interesting stuff, I think. Why also my program in my office is unique in so many ways!
Keep up the good work Fred, love the blogs and information.
In health,
Brandon

palo September 18, 2011 at 11:47 AM
Fred Hahn September 18, 2011 at 12:56 PM

Fritz – I should have been clearer and said that those on VLCD who stall out AND who don’t drink booze, etc. are more than likely falling off the wagon too often and/or eating a lot of processed low carb foods that act on BS as bad as the high carb kind. I also should have mentioned the folks who go low carb but also low fat. I know a few clients who have adopted a LC diet but their doctors scared them off the fat. This too hurts fat loss.

Clare Harding October 3, 2011 at 6:55 AM

People do get extremely worked up when questioning the wisdom of low carb diets. Its hard to believe that the addictive powers of sugar and gluten have not got something to do with it all. All that aside, the question of the role of insulin vs ASP in fat storage is very interesting. I find it very refreshing when conventional ideas are questioned. If we look at the research of Katherine Cianflone it seems that the fatter we are the more ASP we produce, and so the fatter and fatter we get. If this is true, then that is a bummer for the fat! I personally don’t have a problem with both insulin and ASP being responsible for fat storage.

Fred Hahn October 3, 2011 at 10:11 AM

Right Clare – many things are responsible for excessive fat storage just like many things are responsible for muscular growth. But the stimulus for excessive fat storage is chronic insulin elevation and/or chronic hyperinsulinemia in the presence of hyperglycemia. In a nutshell, no chronic insulin elevation, no obesity.

Alan September 6, 2012 at 10:42 PM

Fred you amaze me. I don’t understand how you were able to have a conversation with Carb Sense without completely blowing up. Her attacks and negativity take up the majority of what she writes. I can’t even understand the point she is trying to make half the time because she blabs on and on attacking people and setting the stage for what she wants to talk about without ever getting to the point and I have little patience for horrendous writing. It is also obvious to me that she is posting in her comments section as other people to back herself up.

Fred Hahn September 7, 2012 at 1:01 PM

Alan – patience is a virtue.

Roberto April 29, 2013 at 5:55 AM

Great post, Fred.

Omar Garcia March 26, 2015 at 10:38 AM

Awesome post Fred!! Keep it up with the great Job we see us at the Summit
Cheers
Omar

Kelly October 27, 2015 at 8:06 AM

Nice work. Thank you very much for going the extra mile here.
KT

Fred Hahn October 27, 2015 at 8:32 AM

Thanks Kelly.

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