Monthly Archives: September 2011

Fat Regulation: Insulin or ASP?

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 [[email protected]]
Sent: 11 February 2011 18:49
To: Keith Frayn; [mailto:[email protected]]
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:[email protected]]
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. (https://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:[email protected]om]
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:

https://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:[email protected]]

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.


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