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 is the main regulatory lipid hormone and not insulin. Based on a series of papers and 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“ASP is mentioned in Frayn’s latest version of Metabolic Regulation, but unfortunately texts are woefully outdated.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.
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.
11 February 2011
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
February 12, 2011
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.
Best,
Keith
12 February 2011
Thank you Dr. Frayn.
A blogger I recently read
“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
February 14, 2011 2:45 AM
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
COMMENTS:
gharkness.
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.
Carbsane: So many strawmen, so little time.
Palo:
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.
Alex:
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
Alan:
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.
