This is actually a re-posting of the cited article, but I've updated the post significantly since the original.
Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period Jumana Saleh,* Lucinda K. M. Summers,† Katherine Cianﬂone,1,* Barbara A. Fielding,†Allan D. Sniderman,* and Keith N. Frayn. 1998.
This paper demonstrated ASP actions in vivo for humans in the postprandial (post-meal) period. ASP levels were measured locally to the adipocytes (venous output side) and systemically in the arterial "supply" side. This was important because many who would dismiss the action of ASP look at systemic ASP levels and claim no connection. However, this paper demonstrated otherwise:
The objective of this study was to determine whether Acylation Stimulating Protein (ASP) is generated in vivo by human adipose tissue during the postprandial period. After a fat meal, samples from 12 subjects were obtained (up to 6 h) from an arterialized hand vein and an anterior abdominal wall vein that drains adipose tissue. Veno-arterial (V-A) gradients across the subcutaneous adipose tissue bed were calculated. The data demonstrate that ASP is produced in vivo (positive V-A gradient) with maximal production at 3–5 h postprandially. The plasma triacylglycerol (TAG) clearance was evidenced by a negative V-A gradient. It increased substantially after 3 h and remained prominant until the final time point. There was, therefore, a close temporal coordination between ASP generation and TAG clearance. In contrast, plasma insulin and non-esterified fatty acid (NEFA) had an early (1–2 h) postprandial change. Fatty acid incorporation into adipose tissue (FIAT) was calculated from V-A glycerol and non-esterified fatty acid (NEFA) differences postprandially. FIAT was negative during the first hour, implying net fat mobilization. FIAT then became increasingly positive, implying net fat deposition, and overall followed the same time course as ASP and TAG clearance. There was a direct positive correlation between total ASP production and total FIAT (r 5 0.566, P , 0.05). These data demonstrate that ASP is generated in vivo by human adipocytes and that this process is accentuated postprandially, supporting the concept that ASP plays an important role in clearance of TAG from plasma and fatty acid storage in adipose tissue.—
Unfortunately, the "fat meal" was actually a somewhat balanced meal (although pretty low protein) relatively high in fat and carbs: 60 g fat, 85 g carbohydrate, and 13 g protein = 932 calories total 58% fat / 36% carb / 6% protein. But this actually makes a more compelling argument for ASP regulating/controlling fat accumulation than for insulin when we look at the time course of "fat storage" here.
Insulin and NEFA initially increased in the first 1-2 hr. As stated above, fatty acid incorporation into adipose tissue (FIAT) was NEGATIVE in the first hour indicating net fat mobilization! This seems an odd paradox, but this is not the first study I've read that demonstrated a release (at least initially) of fat from stores in response to a meal. So early in the postprandial period, insulin does not suppress fatty acid release from the fat cells, nor does it send fats on a one way street into the cells. So the high carbs in the meal do not lead to fat accumulation through the actions of insulin. Other research I've blogged on here and here indicates that insulin can stimulate ASP production, although its action is much less potent than chylomicrons. Later in the postprandial period ASP levels increased in the adipose tissue and correlated with triglyceride uptake and net fat accumulation.
At the time of the original posting, I was not aware of who Keith Frayn was, and his name on this paper didn't really mean much to me. Since that time, I've become aware that Taubes cites Frayn in GCBC and Taubes has consulted with him regarding fat metabolism at least in the intervening years since the publication of GCBC. Frayn is "the English guy" who is described by Taubes as an expert in fat metabolism. Indeed he is. Searching the peer review literature that bears his name can rather overwhelm a person with the volume of work. I've shared some of this and have more to come. Thus, given Taubes' claims of rigorous scientific research, he should have been aware of this 1998 paper bearing Frayn's name. This wasn't some obscure rodent study, or in vitro experiment. This study looked at what ACTUALLY happens in live humans after consuming a large (~900 cal, high fat and high carb) meal. The results demonstrate pretty well that Taubes' automaton fat tissue at the ready to accumulate fat in response to glucose and insulin is grossly inaccurate. Instead, net fat accumulation occurs after the insulin response and correlates with ASP which is stimulated largely by the chylomicrons. Yes, insulin can amplify ASP response, but fats stimulate it more.
I am increasingly convinced that Taubes deliberately maintains a state ignorance on such matters as ASP. Because it pretty much demolishes his hypothesis.
In a post entitled WHAT IF LOW CARB IS WRONG? DOES ASP PROVE THAT INSULIN DOESN’T MATTER AND THAT ITS CALORIES THAT REALLY COUNT?, Josef Brandenburg (June 30, 2009) wonders over the significance of ASP and asks Taubes about it. Brandenburg cites the following articles as references for that post: Purification and Characterization of Acylation Stimulating Protein Katherine M. Cianflone, Allan D. Sniderman, Mark J. Walsh, Hai T. Vu, Jean GagnonS, and Miguel A. Rodriguez, 1989; and Metabolic response of Acylation Stimulating Protein to an oral fat load,K. Cianflone, H. Vu, M. Walsh, A. Baldo, and A. Sniderman, 1989. Notice anything? These two 1989 papers were authored by folks whose names one begins to recognize as often associated with Keith Frayn.
One wonders why the "obsessed" Josef Brandenburg (his description) didn't delve a little further into the topic. I've included the authors for a reason, because just a little more intellectual curiosity on the topic would have led to the later works of this group in its varying combinations. But that's why we should always be skeptical of personal trainers peddling scientific theories. Not saying they can't be trusted, but clearly here Brandenburg displays the "scholarly ineptitude" of which Taubes spoke of in our email exchange. I can certainly forgive this of Brandenburg, I could care less unless I were to hire him as a personal trainer. In any case, here were his two conclusions from the papers:
#1. “ASP is far more powerful than insulin in stimulating the creation of new body-fat.” (1)
#2. “ASP is released in response to an oral fat load.” (2)
Brandenburg asks Taubes for his take, from the "Take It Home Gary" section of the post:
“Nice to know you’re suitably obsessed Josef.
“One thing to keep in mind in all this is the need to explain the observations, not just work with possible mechanisms that can’t explain anything. So one of the observations is weight loss on a high fat diet — the Atkins diet.
“So if ASP was good at sequestering dietary fat away in the fat tissue without carbs being needed, why would people lose weight when they ate an Atkins diet?
Ummmm, if insulin was good at sequestering dietary fat away in the fat tissue, why would people lose weight when they ate a low fat diet? As to his question why people lose weight on Atkins ... oh, perhaps ... because they spontaneously, and considerably, reduce caloric intake. Just a thought.
“Another observation we’re trying to understand, as I point out in lectures, is the obesity in poor populations eating low-fat, high carb diets. So there ASP would be irrelevant. Now if we had obesity in populations eating low-carb, high-fat diets, that would be telling and a reason to invoke ASP, but, as far as I know, no such populations exist.
Diverting attention. But what populations get fat eating a low fat high carb diet?
“So maybe ASP plays a role in obesity in rats that are fed high fat diets, but we’re not all that interested in rats.”
I've stated this before in comments on another post, but it really exposes the hypocrisy of Taubes and, indeed, many low carb advocates. That being that rodent studies are applicable when they seem to fit LC the(ory)ology, but not when they don't. I would inquire of Taubes as to why he likes to use that fat rat slide in his lectures if we're not interested in rats after all?
Clearly Taubes is aware of ASP, and if he were actually interested in getting the science right or making good on his "pledge" of sorts to hold himself to the same rigorous standards to which he holds others, he would have followed the names and delved into the research on ASP conducted in the intervening TWENTY YEARS between Brandenburg's articles and his blog post. This is presuming he even bothered to read the 1989 articles. So, how should I class his response in 2009? Umm ... scholarly incompetence for starters.
So the answer to Brandenburg's post title question is YES. The insulin/carb fat accumulation theory is wrong. Fat (net) accumulates when intake exceeds expenditure, and stores (net) diminish when expenditure exceeds intake. Proveably so, and has been since before Taubes even wrote the Big Fat Lie article.