Obesity Related Diabetes & How Gary Taubes has it all Bass Ackwards

Starting sometime in April, I started coming across a deluge of new information related to diabetes -- the classic obesity related T2 diabetes (roughly 80% of T2's are obese, those are the ones I'm talking about here).  There's so much, and by research groups I'd "researched" before, I'm simply amazed I somehow never came across it before.  It's frankly sidetracked me quite a bit from where I was going before the first light bulb over head find, because it all just seemed to fall in place like dominoes fall in some of those intricate arrangements that I'm always intrigued by.  

The first discovery was not in a journal article, however.  It was that I finally got my paws on Lehninger Principles of Biochemistry, 4th Ed (2004) and 5th Ed (2008).    This book is cited frequently by low carbers due to the fact that in recent years Taubes snickers at how stupid the scientists who wrote the book are with two short excerpts he claims are in conflict.  You probably know what I'm talking about, where one quote discusses all the ways insulin puts and keeps fat in cells, and then the next one states something to the effect that obesity is the result of calories in exceeding calories out.   Around that time I came across this interesting, almost memoir, written in 2004 by Richard Hanson.  It's even poignant at times and I enjoyed reading it.  As Taubes tells it, he ran Chapter 22 in GCBC by Hanson (and he's thanked in the credits) and had interviewed him for the book.  A major component of Taubes' Adiposity 101 was the part of this chapter dealing with our old and forgotten molecular friend:  glycerol phosphate aka alpha glycerol phosphate aka glycerol-3-phosphate, I'll call it G3P.

Much as Taubes put a brave face on, and ultimately wrote G3P off as inconsequential.  Even more than insulin I believe, his contention that carbs drive esterification "fixing" fats in the fat cells by making lots of G3P was so key ... he used the phrase "why we get fat" in GCBC based on G3P and this notion that you couldn't store fat without dietary carb.  It would seem that Taubes believed that he had stumbled upon the holy grail of fat tissue metabolism and a mechanism by which carbohydrates were intrinsically fattening.  The G3P = pivotal regulating molecule part of TWICHOO was his "get out of insulin jail free" card.  By that I mean he could defend his hypothesis in the face of the fact that protein also elicits an insulin response, sometimes greater than that of carbohydrate.  The problem, of course, being that protein is pretty routinely regarded not only as a lean tissue building (not fat tissue building) macro, but also as a macro associated with fat loss in clinical weight loss trialss.

It's still amusing to see Gary weigh in with his BS and then get the takes of Carson Chow and Kevin Hall -- our two young biophysicists @NIH, whom I've learned are not quite so young compared to Taubes after all.  These two were after this part of Gary's metabolic BS since at least June 2009.  They had researched every last thing they could to construct their body weight homeostasis model, and concluded that Gary's contention that glucose availability had anything to do with the rate of esterification in fat cells was bunk.  Insulin is also nowhere to be found in their model.  But scientists are not wont to get into public wars with fiction writers science journalists like Taubes.  Still, these two did confront him in a Q&A session once, and as Taubes related in his email to me, it wasn't a very pretty episode for him. In the end, removing G3P gutted WWGF and he wanted it in.  It's really not all that technical (though he repeats how technical and sciencey it is every time he discussed it in lectures).  It was no doubt intended to be in the book in early 2010.

And then along came an anonymous blogger with a whimsical bunny-eared cartoon avatar who pointed out that all one needed to know about what hooey Chapter 22 of GCBC was, was right there in one of his references.  If it wasn't key, I would have been ignored and not seeing my unique page hits roll through the 1 million mark a little while back.  As we see in politics and crime, it is so often not the initial act, but the coverup that sinks you -- and that's where Gary sunk himself too.    In the end he claimed that reference was mostly rat studies and we don't care about rats, that it was just this extra compelling argument but the insulin rules all meme was always his core message, and that what he wrote in 2006-7 was accurate for the state of the science circa 2005 -- and the textbooks were wrong.  (see:  Oh Nevermind)

Bovine feces, plain and simple.  One need no further proof that this man is either a liar or intellectually inept. His textbook -- the one he sourced his diagrams from for earlier lecture slides -- the one he cites as a good summary of it all -- was the 1973 Newsholme & Start text Regulation in Metabolism.  Perhaps if Taubes had written GCBC ten years earlier, he wouldn't have gotten caught misrepresenting this text ... it's long out of print and such books used to be difficult if not impossible to find.  Well, through the glories of the internet I purchased my copy for $3 shipping included.  What I found astounded me.  In no uncertain terms, this book said there was no evidence to support Taubes hypothesis.  None.  In his seminal reference.  Forget the messenger folks, attacking me is ad hominem.  There is nothing more clear as day to demonstrate utter incompetance and intellectual dishonesty than the Newsholme & Start debacle.  None.  He said the texts circa 2005 supported what he wrote in GCBC about G3P being rate limiting and that more glucose = more G3P = increased triglyceride synthesis and thus fat accumulation.  This WAS SPECIFICALLY REFUTED WITH THE WORDS "NO EVIDENCE TO SUPPORT" FOLLOWED BY SEVERAL LINES OF EVIDENCE TO THE CONTRARY.  And this was THE text he cited for this part of the book.  I get the feeling Hanson "forced" Taubes to cite that 2003 paper in hopes someone would follow the crumbs ....

This should be all anyone needs to know about Gary Taubes.  He is incapable of admitting he was wrong, and because he is, he's incapable of being truthful about his current science journalism.  Glyceroneogenesis was on its way to it's well deserved place in discussions of adipose tissue regulation, glucose and lipid metabolism and diabetes.  And as you'll see, Hanson cites in 2004 how his life's work was finally incorporated into what many consider *the* quintessential biochemistry textbook, at least one of the most authoritative references according to Gary Taubes himself.  I've taken screenshots and assembled the section that is so very damning to Mr. Taubes, SBBS (scientist bashing bull shitter).  These are the sections from both the 2004 and 2009 editions so one can see that much of it hasn't changed from 2004.   In the notes on the "new" edition in 2004:

Chapter 21: Lipid Biosynthesis

Features an important new section on glyceroneogenesis and the triacylglycerol cycle between adipose tissue and liver, including their roles in fatty acid metabolism (especially during starvation) and the emergence of thiazolidinediones as regulators of glyceroneogenesis in the treatment of type II diabetes. 

I'm sharing this under fair use through Google docs, here's the link.  No Gary, not only did your 1973 text not "get it wrong", but here is a text circa 2005 that you like to cite these days, that you also, apparently, couldn't be bothered to read, not even an entire chapter or section.  We'll discuss this in more detail in future posts, but the bottom line is that fatty acid release -- the first thing that goes wrong in diabetes -- is regulated largely by re-esterification rates, glyceroneogenesis regulates this, and insulin is not a hormone on the list that regulates this, glucocorticoids like cortisol do.  It's regulated reciprocally in fat and the liver -- the extracellular TAG/FA cycle -- so when NEFA are mobilized from fat, the liver is stimulated to package excess to send them back.  Glyceroneogenesis, and not dietary carbohydrate, is the primary source of G3P and/or how levels are regulated.  TWICHOO was dead before it was written.

So let's see what Taubes tells us about obesity and diabetes -- diabetes being the end-game insulin resistance.    And this is based on TWICHOO v. 1.0.  Excess carbs elicit a high insulin response, and high postprandial insulin release leads to chronic hyperinsulinemia.  The hyperinsulinemia makes you insulin resistant starting in the muscle cells meaning even more glucose gets shunted to the fat cells to make more fat and trap more fat that insulin works to trap there.  Now glucose backs up in circulation and you end up with chronic hyperglycemia.  All of the actions of insulin are "evil" as they serve to make you fat but essentially the precursor of diabetes -- IR -- makes your fat cells go wild.

And now here's what really happens.  For whatever reason -- though most assuredly not because your fat cells went wild triggering a spontaneous horizontal growth spurt -- you take in more calories than are expended, that extra energy is stored as fat.  Insulin helps to clear most of the postprandial carbohydrate primarily into muscle but also into fat.  Fats are cleared in the postprandial phase also with the help of insulin, but also ASP.  The balance of the TAG/FA cycle is tipped in a direction dictated your energy state/needs.

Although not quantitatively significant to overall fat mass, proper glucose uptake and de novo lipogenesis is essential for glucose homeostasis.  As Lehninger points out, T1 diabetics have reduced uptake and conversion to fatty acids.  The de novo lipogenesis produces palmitoleic acid, a MUFA.  There is controversy of exactly what this does -- it's been described as a lipokine (while most hormones are proteins, this is a lipid molecule) with insulin sensitizing properties.  Meanwhile fatty acid release is regulated heavily by the re-esterification process,  controlled through glyceroneogenesis rates, regulated largely by the amount and activity of the PEPCK-C enzyme.   One site for genetic defects is the gene encoding for PEPCK-C.  Small adipocytes have all their glucose-glycerol metabolism intact, as they expand under caloric surplus, they lose it.   Glucose transport/clearance that is usually measured as IR is downregulated into adipocytes by fewer GLUT transporters while the number of these transporters remains normal in muscle.  A defect in glyceroneogenesis -- perhaps as simple as limits on capacity being exceeded -- results in excessive fatty acid release setting the peripheral cascade in motion.  There's evidence that a yet unidentified adipokine stimulates triglyceride synthesis in other tissues to attempt to rectify this.  Excess lipid accumulation in these cells impairs function and glucose uptake -- liver, muscle, and pancreas -- and the pancreas pumps out insulin to compensate.   When the system has been overloaded (not just the pancreas) unchecked hyperglycemia ensues.

Taubes & Co. tell you that insulin resistance starts when you overeat carbs, and all this bad stuff happens in your fat tissue to make you fat:  increase glucose in, increase de novo lipogenesis, increased esterification, decreased lipolysis = fat trapping.  This results in hyperglycemia, glycation, mayhem and death.  What a large body of evidence -- much of which from circa  2004-5 -- is showing is that this is bass ackwards.  The glucose metabolism goes awry -- insufficient uptake and/or de novo lipogenesis and impaired G3P production leading to excess fatty acid release.

And yet some still hang on this idiot's* every word despite clear cut evidence of professional malfeasance.  Lehninger adds to the heap of evidence, but still he writes.  Is it any wonder the scientists, if they attend his lectures at all, will walk out half way through for cheap wine, moldy cheese and stale crackers.  But in that CrossFit lecture Taubes totally disses a man who has given him generously of his time ... dismissing an entire career in one arrogant, snide remark (another giant in the field, Keith Frayn).  All to soldier on defending a hypothesis that should never have been formulated in the first place if he understood how good science is done.  Makes me ill just thinking about this and his protege (who has called a ceasefire in his war on insulin, but is looking to fund more "good science" like the Ebbeling et.al. study he extolls).

The beautiful science really is there Gary.  And much of it is a decade old.   Do we know it all?  No.  Are scientists looking to answer those remaining questions?  Yes.  Most without fanfare or acknowledgement.  I don't know about you, but if I were a diabetic, I would be outraged at the misinformation provided to "help" me in the name of science, and dare I say profit at my expense.  Will Lerner's prediction ever come true?  That some day  instead of guru worship, we'll be hearing "Gary who?"  I can only hope so.

*I feel justified in name calling here, since he has used this term to describe so many of the scientists he's routinely maligned and is totally unjustified in doing so. 


cwaiand said…
how is it people like bernstien and others help diabetics by basically following(and confirming)the insulin hypothosis?a real question,would like your take.
CarbSane said…
Two part answer depending on type of diabetes (1 v. 2) -- but it boils down to the LC approach managing the symptoms, or as Wheat Belly describes it as putting diabetes into remission. I would say if you're talking T2, remission is not an appropriate word, you're still managing the hyperglycemia.

I spent a lot of time on Jimmy's forum back in 09 and there were a lot of diabetics there. They sing the praises of LC curing their diabetes. For those for whom this is true, it is almost always accompanied by sustained significant weight loss. But many of these people report with high frequency becoming less and less tolerant of any sort of glucose challenge, IOW once weight stable their IR comes back particularly if they're restricting protein and eating a ton of saturated fat (or just fat at that point). Long term low carbers who didn't have IR before become glucose intolerant -- Tom Naughton is a perfect example and Jimmy Moore to a lesser extent. Naughton claims a potato would send his glucose through the roof, yet he had no signs of glucose intolerance in Fat Head. Jimmy was, if anything, a little on the low side for fasting insulin and had a perfectly normal insulin response in 2008 to a large low carb high fat & protein meal. But his fasting glucose levels have crept up.

In any case, liver IR has to progress past a tipping point for the pre-diabetic to frank diabetes, so until that time, LC manages pp hyperglycemia (though you see folks with inappropriate rises due carb free meals due to LIRKO-style lack of inhibition of gluconeogenesis).

Bernstein is a fan of the metformin so that keeps the GNG in check, and as a T1 takes insulin. LC with low insulin manages hyperglycemia. Since this person's beta cells are never going to come back, and they have to take insulin, his position is that if you keep things in small doses of carb then small predictable doses of insulin should keep your stable control simpler.

His approach to T2 is not unlike taking medications to control blood sugar. Again, Bernstein is a big fan of the metformin for the FBG and if you don't eat many carbs it's just not likely (especially early on) for a little unchecked GNG to raise blood sugar too high after a meal. Give this person a bowl of oatmeal or a potato and their bodies cannot respond appropriately. (1) If you don't use it you lose it, e.g. enzymes and genes for expressing them and whatever for synthesizing hormones all get down regulated. and (2) Your free fatty acid problem is not helped and may well be exacerbated by your diet. The disease is thus progressing with your false security that you are (thus far) keeping glucose in control.

T2 is reversible in far more cases than anyone could ever imagine with drastic intervention. Reversible in that the person has normal glucose homeostasis, not just an ability to keep BG under 150.

Bernstein, Davis and others aren't confirming TWICHOO, they are confirming that one way to manage blood glucose is to not have much if any from the diet, and (usually) take metformin for the GNG. It's like treating a fever by staying out of hot rooms or taking cool baths, but the source of the fever will not go away from these measures, and it might be counterproductive as the fever is the body's way of trying to fix the problem. Or you can take a course of antibiotics and eradicate the cause and maintain body temperature again.
cwaiand said…
then some of these cyclical bodybuilding type diets would work well on type 2.low carb 6 days a week to control blood sugars and then a moderate carb load to replenish glycogen and keep the system working(use it so don,t lose it).maybe?
Unknown said…
I would like to see an expose on the "fat burning beast" versus "carb burner" thing because Sisson is laying it on pretty thick.
Craig said…
@ Carbsane:

I wonder if you have ever spent any time on the 'very low fat' diet forums (e.g., McDougall).

They claim that a very low fat diet coupled with weight loss restores insulin sensitivity and (sometimes) cures T2 Diabetes. But as I look at the links to studies they cite, and see self reported results, I don't get a clear sense of whether or not there are that many people who really achieve normal glucose metabolism. Not that there aren't some - I recall a former T2 diabetic losing a ton of weight and claiming to maintain an A1C <5.0, while eating such a regime. I just can't tell how many people really achieve such a result. Jenny over at diabetes update seems pretty sure that they are rare and that relatively few low fat folks actually achieve anything like good glucose control or normal glucose response. Wondered if you had any feel for this.
Manythings said…
What would be like antibiotics to maintain body temperature again - how can I eradicate the cause of Type 2 diabetes? Would you mind a further question - what is the cause of Type 2 diabetes?
Many thanks.
CarbSane said…
I have not, but there are two or three readers here who've commented from time to time about following DASH and some other plan, perhaps even McDougall. Funny, I was checking up on my friends the other day and they're discussing McDougall at Jimmy's. He makes the claim I made sort of tongue in cheek a little while ago -- that there's no dietary need for fats besides EFA's because our body can make them. I don't think his detractors realize how silly they seem for knocking that particular claim.

When looking at some of Rosedale's claims I was alerted to and/or came across myself several studies of very high carb, very low fat demonstrating insulin sensitizing. I would also note that the traditional Pima were "sprightly" and free of diabetes on a very high carb, single digit fat and protein diet.
CarbSane said…
Yeah, it's just a shifting gimmick IMO. I don't plan to make a nuisance out of myself at AHS, but I will ask what evidence there is that fat is a preferred or cleaner burning fuel. Seems just the opposite to me!
CarbSane said…
@cwaiand: Yes, cyclic would seem to have benefit -- I do have concerns with those who essentially binge on feed days though and may eat very high fat the other days. I don't know that our bodies can switch it up that fast. Due to how I lost my weight this was an issue for me and one of the questions I sought to answer -- would it be better to adopt a more moderate carb consistent diet, or was VLC with occasional cheats OK.
CarbSane said…
First, it's not a perfect analogy, but it will do. It really does seem that the "it starts in the fat" holds up quite well in the pathogenesis of diabetes. It's quibbling sometimes I suppose because the first place we may "see" the effects is from liver IR, but I think this is because NEFA are so difficult to assess they are not routinely measured, and adipokines, even leptin, are not regularly measured either.

But ultimately to eradicate it, we need to reverse things back to what started in the adipocyte, and most of the time that's shrinking them. The faster the better (you're newer here, I'd check the chrono list of posts and look for the posts on gastric bypass and diabetes, and the crash diets and diabetes). I've yet to see one iota of proof to the adage that once you're diagnosed half your beta cells have already bought the farm. Rapid restoration of glucose tolerance in very short orders pretty much refutes that. Early insulin therapy has also helped, and I imagine that class of drugs that upregulate glyceroneogenesis (thiazsumpthing) and lower fatty acids should help as well.

I don't think we know the cause, but clearly some are genetically vulnerable. The reason LC at maintenance may make matters worse is that it doesn't help with fatty acid trapping, and DNL, trig bundling in the liver, etc. are all downregulated. There are animal studies showing diabetes progressing on keto diets. Not sure what to make of those, but I'd like to play it safe :-) There are certainly diabetics who swear by VLC and Bernstein. But IR in and of itself is a risk factor for CVD even when normoglycemic (e.g. compensating).
Sue said…
Like the very low calorie diet study on diabetics who lost weight and improved. Its the losing weight and using up the NEFA.
bentleyj74 said…
Hopefully you aren't planning on asking Sisson since he's about as qualified as I am to answer. He could respond by bending over to tie his shoes and maintain the same level of credibility.

Seriously though, if you were going to ask...who would you ask? I'd possibly be interested in their answer.
v/vmary said…
i had the same question as manythings, but i didn't understand the answer. can you put in some examples and dumb it down a little? Like "this person started out life blah blah blah, and then they started with _____behavior which led to _____.

i'm very interested in this because although i don't have diabetes, both my parents do. both parents and 2 daughters and 1 son all gain weight on their stomach the most. the other son is thin even at 46.

like i said in a previous comment, i've lost a lot of weight, but i still have some to lose. i'm wondering just how dangerous that remaining weight is (lower ab fat). my sister has a huge stomach, but says all her blood numbers are good.? right now i'm more curious than concerned, but i like to learn all i can. thx.
Manythings said…
Many thanks for your reply. I posted a further question last night (well, I thought I had!) but it has not come up. I'll try another go ... basically, how can I eradicate Type 2 diabetes? Gastric surgery is not acceptable to me - I would rather just eat less! If crash diets work, I would certainly be happy to try that. If low calorie is the answer, should it be higher carb and lower fat than LC? I guess that too much protein is not the answer, as that just turns to glucose in the liver.
Thanks again (hoping that I manage to post correctly this time)
CarbSane said…
I checked spam, sometimes posts just don't go through, and this seems to have happened to you. Sorry about that.

Your thoughts on GBP are certainly understandable. This post might help for an overall view: http://carbsanity.blogspot.com/2012/02/my-sump-pump-analogy-for-cell.html
Blogs on crash dieting to reverse diabetes: http://carbsanity.blogspot.com/2011/07/diabetes-crash-cure-pancreatic-fat.html

I don't think I blogged on the early insulin therapy, here's the study

A number of trials have evaluated the strategy of implementing short-term aggressive insulin replacement as first-line therapy in the management of hyperglycemia in newly diagnosed type 2 diabetes (Table 1), with the goal of improving and preserving β-cell function, reducing insulin resistance, and maintaining optimal glycemic control through disease “remission” (16–18). In these studies, intensive insulin therapy was delivered via multiple daily insulin injections, or insulin pump therapy (continuous subcutaneous insulin infusion), over a period of 2–3 weeks, with achievement of euglycemia in ∼90% of subjects on completion of insulin treatment. After insulin withdrawal, patients were maintained on diet therapy only, with 42–69% maintaining euglycemia 12 or more months after treatment.

Rosedale says insulin should never be used with T2's.

Are you diabetic? If it were me, I'd work with my doctor and give a crash diet or EIT a try. What have you really got to lose? It's NOT going to harm you. Note the EIT timeframe -- 2-3 weeks!!! This "bought" normoglycemia for a year or more for around half of responders.
CarbSane said…
P.S. The very low cal diets used are essentially protein-sparing modified fasts. Protein is insulin sensitizing as well.
CarbSane said…
I think the best we can do is avoid chronic caloric excesses. There's no one food or macro that "causes" diabetes and although 80% of T2's are obese (the only sort I'm addressing here), 20%* of obese are metabolically normal (and countless others are some degree of IR but "compensating" and relatively normoglycemic).

I guess the overarching point of this post was that carbs and all of the bad things insulin is supposed to do with them, do NOT cause diabetes. It's when insulin doesn't do with them what it's supposed to in the fat cells that you're set rolling down the hill to diabetes.

This is anecdotal but instructive IMO. When long term low carbers admit to having trouble keeping fasting glucose levels under control despite eating VLC religiously, Houston we have a problem and we have evidence (why would they lie about this?) that the adaptation is unfavorable for insulin sensitivity in the liver. PeterD likes to talk about FIRKO-izing via keto diet though there's no evidence of any similarities. OTOH, keto diets do seem to LIRKO-ize in animal studies.

The Inuit were not in "nutritional ketosis" being pushed lately. Not even close. They are the only humans living today or in recent enough human history to know for sure how their diet impacted their health.
CarbSane said…
I don't think Sisson is presenting, he's participating only on a paleo/primal roundtable I think. I've got to look at the abstracts -- should be up soon or maybe they are ... I just don't check back regularly.
CarbSane said…
What's weird is that you do early insulin therapy, patients perhaps even gain a bit, but it goes into remission. You do GBP, and glucose homeostasis is attained in days to short weeks before considerable weight loss. You do crash diet, it's rapid weight loss that de-fats the pancreas (mechanism?) in a longer period (though glucose resolves sometimes shorter. Fascinating to me.
CarbSane said…
This comment has been removed by the author.
Manythings said…
Not diabetic, but I had a nasty case of metabolic syndrome. I have lost 55lb in the last 18 months or so and (at least on a BMI basis) am now bang in the middle of a healthy weight (down from just across the obesity line on the BMI graph). I lost the weight because I did not want any progression to diabetes (or any other of the diseases associated with metabolic syndrome). I am eating quite low calorie, low carb, moderate protein and high-ish fat (I use Jennie's calculator) and my weight loss has pretty much stabilised. I am wondering now what is the best diet to maintain this weight and continue to reduce the risk of diabetes, so am open to ideas about whether there is any better maintenance diet than the one I am using now. In particular, I wonder this - if I am eating exactly the number of calories I need to maintain my weight, and exactly the amount of protein I need for muscles etc., then what difference does it make whether I balance the protein with fat, carbohydrate or a mixture of both (for energy)? If they are going to be burned up right away as fuel, does it ven matter?
Galina L. said…
I want to address that highish FBG on VLC diet. Mine was always between high 80-low 90 on a mixed diet, after the end of the year when I gained 26 lb in a year, started to have abnormal amount of migraines , flues and bacterial infections, it raised to 99. After I adopted LC diet, it fell to 72, after I got adapted to IF,1.5 years ago, it raised to 107 - 110. I experience no negative changes in health, only the increase endurance during exercise.
Galina L. said…
Macrocomposition matters as well as the amount of calories. For example, there are a lot of people who don't feel right on a high-protein-lc-low-fat diet.
Scott Russell said…
Looking at the chapter you linked (thanks for that btw, been trying to get my hands on a biochem book for cheap) glyceroneogenesis is regulated primarily by levels of PEP carboxykinase in the respective tissues. The regulation of PEP carboxykinase in the liver is regulated by glucocorticoids, true, but regulation of PEPCK in adiposites is regulated by insulin.

I realize you are very anti-Taubes, but I cant help but feel like much of this ire is unwarranted. No, he did not get all of the biochemistry right, but I wouldn't jump to calling this outright deception. From when I have heard him talk in interviews, etc, he seems more interested in removing the calories in/calories out ideology, and he simply leans towards the insulin idea because that was what made sense to him.

Re: FBG on low carb, this makes sense in my mind. Low carb doesn't just lower insulin levels, it also induces physiological insulin resistance. This spares glucose for the brain. Elevated FBG should be viewed in light of the body's relative sensitivity to insulin.
CarbSane said…
Gee, you're welcome. Too bad you didn't bother to read that chapter that you've been trying to get your hands on. Where does it say PEPCK is regulated in the adiposites (sic) by insulin? It does not. Heck, you don't even need to read, they drew you a nice picture in Fig 22-2 (5ed). Do you see insulin there?

Gary Taubes is a hack. He has no clue WTF he's talking about, he doesn't understand the science so he doesn't even read the textbooks he cites. He gets MOST of the metabolic regulation of biochemistry wrong, and presents only the most rudimentary biochemistry out of context.

His theories make sense to him or any of us how? He's trying to talk good science and testing hypotheses. TWICHOO fails every test repeatedly. Most of that testing done and even appearing in textbooks well prior to GCBC.

Of course elevated FBG "makes sense" -- but here's my point. Low carbers hail to the heavens over lower fasting trigs and blast carbs when they fail to lower them or raise them. Because on the SAD micro ratio, elevated trigs are part of an atherogenic profile. Well, so too is elevated FBG. Can't have it both ways. See? Or maybe it means nothing ... or maybe it's a tilt in the wrong direction.
Scott Russell said…
Sorry I forgot to cite: http://www.ncbi.nlm.nih.gov/pubmed/2166335
or http://www.ncbi.nlm.nih.gov/pubmed/7980440
Its also on the wikipedia page, fwiw.

Not pretending to be an expert, but insulin is essentially the "food signal," so it makes sense that it would play a major role in how much G3P needs to be made. And in the fed state, we dont need glyceroneogenesis to supply DHAP. Or maybe (probably) I'm missing something?

Not trying to defend "low carbers" in general, or sing Taubes' praises, but I found his book very informative, and I dont consider him a hack. But agree to disagree I suppose.

I'll admit low carbers tend to jump on things that support them and downplay those that dont, but then again, it seems like everyone does that.

My point with FBG was simply that we always need to keep things in context. Its easy for people to become hesitant when they see "negative" biomarkers, without considering why the biomarkers might be changing. By all means, even lowering fasting trigs isn't necessarily a good thing, if it is simply indicative of worsening fatty liver.
CarbSane said…
Both of those cites refer to GLUCOneogenesis, not GLYCEROneogenesis. Huge difference as gluconeogenesis doesn't even occur in adipocytes. That's what fascinated the real scientists so much that they discovered the process. Fat cells don't make glucose and they also lack certain enzymes in that pathway. So what was PEPCK-C doing there? And they also have some small amounts of glycerol kinase to make G3P from glycerol but it's insignificant amounts. The G3P is made by glyceroneogenesis and this is regulated by glucocorticoids in liver and adipose. Insulin may well regulate hepatic glyceroneogenesis because of the shared enzyme, but heck ... if it were up to Gary Taubes nobody would even know about GLYCEROneogenesis.

He has no idea what he's talking about. If I challenged him to a head to head debate he would decline and say he's just too busy. Maybe we should take up a collection to pay him to do it. Then when he declines because he couldn't hold up his end, we could finally move on from his BS version of adipocyte metabolism and obesity and really advance the science.

There's a reason his science is ignored. Most of it has been disproven or it is taken so out of context he should be ashamed to even present it that way. Yep, I'm in a bit of a mood today :D
Scott Russell said…
Well sure they were studying PEPCK in the context of gluconeogenesis, but its the same enzyme that regulates both processes.

I'm just not so certain how relevant glyceroneogenesis is to someone who is interested in loosing weight. It is an elegant system for maintaining the cycling of fatty acids while fasting, but it only seems to be relevant while fasting, and doesn't seem to inhibit fatty acid availability.

I think there might still be something to the idea that a lack of dietary carbohydrate limits the availability of substrate for G3P. We can clearly manufacture some of it, but can we make enough to become obese?

No doubt Taubes oversimplified, but I think Taubes is doing more good than harm. I just dont get the Taubes bashing, but w/e.
CarbSane said…
Why do you cling so? Carson and Hall read every paper on the subject when developing their metabolic model and apparently forwarded them to Taubes. Why do you think there might still be something to an idea that Taubes' own 1973 reference -- that he cited as a good discussion of the topic -- said THERE WAS NO EVIDENCE TO SUPPORT?

Taubes did more than oversimplify. He didn't do due diligence and when caught in the act he lied. LIED.

There's nothing about his hypothesis that withstands the light of existing science. Nothing. This is why scientists walk out on his lectures.
Scott Russell said…
Sorry, I was really more interested in glyceroneogenesis than whether or not taubes is dr evil.
CarbSane said…
This comment has been removed by the author.
CarbSane said…
BTW, see what you just did there? You thanked me for the biochemistry text excerpts because you apparently had an interest in these things. Then you stated definitively that insulin regulates PEPCK in fat cells despite there being no such mention in the biochemistry text. Then when I pointed this out, you gave me two citations regarding PEPCK in the liver and gluconeogenesis. And now of course insulin regulates it because it's the same enzyme. Really? Then why is the same enzyme regulated in reciprocal fashion by the same hormones in liver and WAT? It's not just the enzyme. Glyceroneogenesis is a major source for G3P in the liver but the pathways share enzymes. This may well be why trigs are lower in low carbers for better or worse. Or PEPCK (there's more than one enyzyme that goes by this) may be compartmentalized or differentially regulated by the same hormone -- ya know, like all LPL's don't respond the same way to insulin?!!??!!

Oh ... but never mind. Taubes has done more good than bad, and you were interested in glyceroneogenesis? Really? Then why didn't you bother to read what has been written here about it and post links about gluconeogenesis and its regulation when gluconeogenesis doesn't even occur in fat cells???????? Do you want to learn about it or are you just interested in attacking me for exposing Taubes. Don't bother answering, though it would be entertaining.
Scott Russell said…
Sorry, really not trying to incite anger here, and I apologize if I've done so.

Quite possible I'm oversimplifying, but in my mind:
PEPCK limits the rate of both gluco and glyco-neogenesis. So no matter the stimulus, the levels of PEPCK are what matter.

I got the impression that PEPCK (at least in the context of gluconeogenesis in the liver) is regulated by insulin in the sense that insulin controls the transcription of glucocorticoid receptors. So insulin goes up, glucocorticoids go down, and the subsequent PEPCK changes occur. In the liver this means less PEPCK, meaning less gluconeogenesis. Would this not also mean less glyceroneogenesis?

The reciprocal effect I would expect to be similar in adipose tissue. Insulin goes up, glucocorticoid transcription goes down, and PEPCK levels increase. This leads to increased glyceroneogensis (right?) Gluconeogenesis doesn't occur, but that doesn't seem to matter, if the issue is control of PEPCK through glucocorticoids.

So insulin seems to still be a primary controller, even though the text doesn't discuss it. Or did I make an unwarranted leap of logic somewhere?
CarbSane said…
The reaction you are perceiving as anger is not anger. It is profound frustration. I feel like it's deja vu all over again two years later.

If we're talking Taubes' version of fat mass regulation, we focus only on the adipocyte intracellular cycle. http://tinyurl.com/adipocyteTAG-FA You keep talking to me about PEPCK in the liver. In the liver this enzyme is part of the gluco and glyceroneogenesis pathways. In the adipocyte there is NO gluconeogenesis -- it specifically regulates the glyceroneogenesis pathway.

The same hormones do opposite things to the same enzyme in different tissues, even different fat types. If you want to play that game, insulin downregulates gluconeogenesis so it should downregulate glyceroneogenesis in the adipocyte, right?

This is what Lehninger Principles of Biochemistry is saying. The giant leap of faith you are making is not accepting that the book makes no such claim as insulin still seeming to be the primary controller.

"I think there might still be something to the idea that a lack of dietary carbohydrate limits the availability of substrate for G3P. We can clearly manufacture some of it, but can we make enough to become obese?"

Yes we can. And we can store fat without dietary carbohydrate. I feel like I'm talking to Fred Hahn again. The hyperglycemia in diabetes is due to unchecked gluconeogenesis in the liver. PLEASE read the following article in its entirety: http://bja.oxfordjournals.org/content/85/1/69.full

This is why Taubes should have at least written on his blog that most of Chapter 22 of GCBC was wrong. You need G3P but as he stated in one interview, Hall & Chow told him there's always enough around to do the job. Newsholme & Start (his seminal reference for this) says there's NO ... repeat ... NO evidence to support the idea that increased glucose -> increased G3P -> increased esterification ... and then they go on to list the evidence against that idea. In 1973. In a textbook Taubes cites and used figures from for his earlier lectures.

to be continued ...
CarbSane said…
The purpose of the TAG/FA cycle in the adipocytes is to regulate NEFA in circulation. Insulin, glucocorticoids and ASP all act on this cycle to regulate NEFA to (along with glucose) meet the needs of the organism (e.g. activity level, dietary influx). What determines if more fatty acids eventually end up in the fat cells is energy balance. Good old CICO, and while hormones obviously play a role in adaptations to deliberate attempts to alter CICO (e.g. ELMM), insulin does not appear to be one of them. Taubes even mentions that more NEFA are released than are used, and often sounds a little stilted when he does, because I think he hopes nobody notices -- that what's not used is sent back to the fat tissue! NEFA are in circulation and taken up by cells and excess -- large excesses -- are released all the time. The liver's job in this regard is to package them up to VLDL and send it back to sender. The vast majority of triglycerides secreted by the liver are comprised of NEFA: http://carbsanity.blogspot.com/2011/05/where-do-triglycerides-come-from-part-i.html

Gary Taubes has taught you "black age" endocrinology on top of hypotheses of the likes of Bauer and Neels as if they were tested and accepted, and apparently didn't read and/or understand his references. He's a journalist with a scientific background in no way related to the biochemistry, physiology and metabolism. If you genuinely want to understand these topics, may I suggest a book you can buy an older edition of for quite cheap? It's Nutrition by Insel, Turner and Ross. I have the 2001 version with Wheat on the cover. There's some nutritional advice in there some may find objectionable, but despite the title, the discussions of physiology, digestion, metabolism, and basics of biochemistry is really quite good. It is written at a level I think many would find readable and understandable. It's a good first start. I stumbled upon it once because I was searching on Marc Hellerstein and it has a section on the whole "do carbs turn into fat" question.

How many of today's low carb "experts" are still telling people that the liver takes up carbohydrates and turns them into fat. How many of these were inspired by Gary Taubes or learned this from him despite possessing degrees in Biology themselves. How many learned their biochemistry from Gary Taubes instead of going back to their textbooks from medical school. How many people believed Chapter 22 in GCBC -- that they couldn't get fat w/o dietary carb and spent years trying to tweak their low carb diet and gaining weight (either because they were still eating too much or they could not sustain the tweaks). It is sickening Mr/Ms? Iced Coffee.
CarbSane said…
Galina, if macro differences make you feel better and increase NEAT then I suppose one could say they matter. When you think about if there is a boost in NEAT, that's only "non-exercise" because its not deliberate, but wouldn't all that activity just make you hungry and eat more?
Scott Russell said…
Thanks for the link, some interesting stuff there. Definitely a solid review.

The reason I mentioned PEPCK liver studies was simply that they suggested that the method by which insulin regulated PEPCK in the liver was through control of glucocorticoid receptors. I was under the impression that the inhibitory affect of insulin on glucocorticoids was systemic, so logically it would provide a similarly inhibitory affect on glucocorticoids at the fat cell.

Thanks for the textbook ref, I'll look into it.
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