The Carb-Sane Asylum

A short "image park" in my ongoing effort to document the state of the textbook science of fat storage, obesity and adipocyte function circa the writing of a three PhD thesis worthy tome.   This from Marks' Basic Medical Biochemistry , 2nd Edition, 2005.  Thus, although activation of hormone-sensitive lipase during fasting results in the release of fatty acids from adipocytes, the release is carefully modulated through glyceroneogenesis and re-synthesis of triglycerides.

So Jimmy Moore has released his latest lipid panels , after losing 50-or-so pounds in 5 or so months of his nutritional ketosis experiment.  Before I comment on these, a huge revelation was made in the post: Interestingly, before I started on the Atkins diet in January 2004, my highest total cholesterol was only about 230. Of course, my doctor put me on both Lipitor and Crestor to lower that number and it did get down to 130 at some point (don’t know what the breakdown was of HDL and LDL nor do I know what my triglycerides or LDL-P were at the time either). Ummm ... Jimmy, do you even bother to look back at your own blog? Seems not, which is a darned pity for someone so darned and determined to figure all of this out, but who doesn't even look at his own data.   Before I started livin’ la vida low-carb , my HDL was a dismal 21 and my triglycerides hovered over 250. My LDL was about 250 which brought my total cholesterol to around 275. It wasn’t a pretty picture.

Thanks to a certain journalist, much of the discussion of fat tissue metabolism on the internet presents a very myopic view of things taken out of context.  One example of this, is that in Chapter 22 of GCBC, Taubes lists all of the hormones acting on adipocytes.  The caption on the graphic reads: In 1965, hormonal regulation of adipose tissue looked like this: at least eight hormones that worked to release fat from the adipose tissue and one, insulin, that worked to put it there. Let's leave aside for a moment that in the four subsequent decades preceding the writing and publication of his book, probably the most potent regulatory hormone of fat mass, leptin, was discovered.  Let's also leave aside all of the other adipokines (the term for the collection of hormones and peptides produced by adipocytes most of which appear to be secreted).   There's a lesson to be learned solely from Taubes' narrow, outdated view.  Under the title "Hormones that promo...

I'm really rather amazed that at this point we're still having to discuss this topic.  As a good friend of mine once said to me in an email (paraphrasing):  One would expect these sorts of myths to persist back in the 80's and 90's.  But in this day and age of information availability on the internet, it seems impossible that enough people continue to be influenced by such easily debunked notions.  Low carb Wiener anyone? {grin} In any case, it seems that no amount of demonstrating the lack of any correlation between fasting insulin levels and weight loss will convince some people.  I really would think that the scatterplot (weight loss v. fasting insulin), discussed in this post ,  would be impossible to explain away, and yet many just dismissed it from their minds.  It's that proverbial black swan all the Eades Popperites (or is that all you can eat (Eade) sous vide popper-bites?) constantly seek.  

Ketogenic diet-fed rats have increased fat mass and phosphoenolpyruvate carboxykinase activity This study looked at body weight, fat mass, blood lipid and glucose levels and PEPCK (rate limiting enzyme in glyceroneogenesis pathway for G3P production for esterification of fatty acids - fat deposition) activity in the liver and fat cells.  Two ad libitum diets were compared, a control standard chow and a ketogenic zero carb chow.  This study was in normal, young (30 days old at start) Wistar rats and lasted 6 weeks. The diet compositions are shown below:

Non-esterified fatty acid metabolism and postprandial lipaemia Yet another gem from ... who else? ... Keith Frayn! Non-esterified fatty acids (NEFA, or free fatty acids) are an important metabolic fuel. Both the concentration of NEFA and their flux through the circulation vary widely from hour to hour, reflecting nutritional state and physical activity. Inappropriately elevated plasma NEFA concentrations may have a number of adverse effects on both carbohydrate and lipid metabolism. As my regular readers know well, this is a focus of my research. These adverse effects are likely to be most marked in the postprandial period, when NEFA release from adipose tissue is usually suppressed. Although the regulation of NEFA release in the postabsorptive state is well understood in molecular terms, the predominant pathway for release of NEFA in the postprandial state is the action of lipoprotein lipase (LPL) in adipose tissue capillaries on chylomicron-triacylglycerol...

In his most recent interview with Jimmy Moore , Gary Taubes did a bit of a mea culpa on the notion that dietary carbs are required to store fat.   He offers up a rather weak description of how he got it wrong for so long in his lectures ("skewed") and claims this wasn't something from the book but rather the lectures. Originally my post here stated that strictly speaking this was true, but upon rereading those sections of GCBC it is quite obviously not.  One could even go so far as to say it is the lynchpin of his hypothesis, but that is open to interpretation.  Still, Taubes repeated in the interview that G3P is "rate limiting" in the esterification process, a claim he made unequivocally  in GCBC.   Here's the relevant paragraph: A single molecule plays the pivotal role in the system.  It goes by a number of names, the simplest being glycerol phosphate.  This glycerol-phosphate molecule is produced from glucose when it is used for fuel in the fat ...

Glyceroneogenesis Is the Dominant Pathway for Triglyceride Glycerol Synthesis in Vivo in the Rat* OK ... yes, this is a rat study, but the body of work by Hanson's group has demonstrated that the results obtained for the rat correlate well with human metabolism.  These studies utilized radiolabeling "tracer" methods to track the substrate source for G3P.  Three dietary groups were compared: 1.  Controls - regular chow fed (removed 7am study morning) 2.  48 hour fasted (food removed 48 hrs prior) 3.  Lipogenic (high sucrose) diet (5 day sucrose water in addition to regular chow and glucose infusion during testing to "maintain the lipogenic state"). The abstract is long so I'll let y'all readers just read it at the source if you like.  I'll focus this post on excerpts from the discussion of the results. Plasma:   The plasma concentration of triglyceride were not different in the three groups ( Table 1 ). The fraction of plasma triglyceride glycero...

I was recently invited by Jimmy Moore to appear on his podcast in response to some of my recent posts on Gary Taubes' most recent lecture and his interview with Jimmy.  This elicited the following email to me from Gary Taubes.  (Aside:  My email is open to anyone who wishes to use it through my profile here).  At his request, I have included it in its entirety here along with my responses.  Taubes' words are in default font, my responses are in green italics. ************************************************ Hi Carb Sane,    I hope you don't mind me taking the liberty of e-mailing you. Jimmy Moore told me that you might be going on his show,  which prompted me to try to read a few of your latest blog entries. Occasionally, friends have suggested I read and respond to your critiques (attacks?) , but whenever I try I find them tough going. Your descriptions of what I wrote or said or argued never quite seem to mesh with what I actually wrote or s...

The detractors of energy balance theory often say something along the lines that thermodynamics goes out the window in living organisms, the rules don't apply.  Nope.  The existence of the Second Law does not violate the First Law! This simply isn't true, and those who say similar must simply not understand these fields.  Humans are not bomb calorimeters or Carnot cycle/combustion engines .  When Dr. Eades tried to discredit Anthony Colpo a while back, he and his compadre Feinman waxed poetic and evoked nightmares of steam tables in their college thermo courses.

My greatest criticism of Taubes is that despite several years of "exhaustive" research, and a deluge of references in his book, the bulk of his "Adiposity 101" is either unreferenced, or based on decades old physiology texts and papers. In this lecture (Slide 48 at around 46 min in) is his discussion of glycerol-3-P.  Taubes is a master of stating facts ... in a misleading way that (1) leads the listener/reader to incorrect conclusions, and (2) enables Taubes to use the "I never said that" out when challenged. He first quotes a 1970's text on the Fatty Acid Cycle and shows an updated text of similar.  In both he highlights the need for glycerol-3-P to esterify FFA's to triglycerides.  This is true.   However on Slide 48 he presents a bunch of cobbled together "facts" that are either not considered settled science or are taken out of context.  And I note that while he now (2009) lists glyceroneogenesis on his slide, the word ...

Glyceroneogenesis and the Source of Glycerol for Hepatic Triacylglycerol Synthesis in Humans Glyceroneogenesis, i.e . the synthesis of the glycerol moiety of triacylglycerol from pyruvate, has been suggested to be quantitatively important in both the liver and adipose tissue during fasting. However, the actual contribution of glyceroneogenesis to triacylglycerol synthesis has not been quantified in vivo in human studies. In the present study we have measured the contribution of glycerol and pyruvate to in vivo synthesis of hepatic triacylglycerol in nonpregnant and pregnant women after an overnight fast.  After a 16-h fast, ∼6.1% of the plasma triacylglycerol pool was derived from plasma glycerol, whereas 10 to 60% was derived from pyruvate in nonpregnant women and pregnant women early in gestation. Our data suggest that glyceroneogenesis from pyruvate is quantitatively a major contributor to plasma triacylglycerol synthesis and may be important for the regulati...

http://pepck-and-the-ketogenic-diet.com/index.html There's some interesting information on this -- apparently -- "amateur" website.  PEPCK is an important enzyme regulating blood glucose and free fatty acid levels.  It is involved in gluconeogenesis and glyceroneogenesis.

Everyone who believes Taubes' theories about Glycerol-3-P and not being able to store fat if you don't ingest dietary carbs should read this article. Glyceroneogenesis and the Triglyceride/Fatty Acid Cycle We make glucose via gluconeogenesis.  So, too, we make glycerol via glyceroneogenesis.  And we recycle ~50-65% of the FA's released via lipolysis back to trigs. One interesting thing is the behavior of brown adipose tissue.  The enzyme responsible for re-esterification, PEPCK-C is high in BAT.  But interestingly enough insulin INHIBITS this enzyme while a high protein zero carb diet stimulates it.   There's lots more  here to digest.  I'll revisit this post and update.