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 glycerol derived from glyceroneogenesis was ∼60% and not different among the three groups (Table 1). Approximately 15% of triglyceride glycerol was derived from glucose in the control group (Table 1). The contribution of glucose was lower in 48-h fasted rats (∼11%) and was higher in sucrose-supplemented animals (∼28%). Although sucrose supplementation resulted in a higher contribution of glucose to plasma triglyceride glycerol when compared with controls, the contribution of glucose was less than that of glyceroneogenesis (Table 1).
The highlighted statements say it all. No difference in triglycerides or the fraction of those triglycerides formed using glyceroneogenesis-derived G3P between the groups.
Glyceroneogenesis and Glycolysis as G3P source in Adipose Tissue: There was no significant (p = ns) difference in the triglyceride concentration in the adipose tissue of controls and 48-h-fasted animals. In the sucrose-supplemented animals, the concentration of triglyceride was significantly higher than controls (Table 2).
FAT ACCUMULATION OCCURRED IN THE SUCROSE-SUPPLEMENTED RATS ONLY. CARBY CHOW-FED RATS DID NOT ACCUMULATE FAT
Note: It is important to remember that one way human and rat metabolisms differ considerably is in the rate of de novo lipogenesis (aka converting excess carbs to fat) and it's contribution to fat stores - that being that DNL is not a major pathway in humans for fat storage (see my DNL label for some posts on this) but is in rats. It is also important to note the use of the word "supplemented": e.g. the sucrose rats were getting an excess.
This section continues:
... The rate of glyceroneogenesis in the control animals was ∼600 nmol/g/h in the epididymal adipose depot and ∼800 nmol/g/h in the mesenteric depot (Table 2). Glyceroneogenesis did not change in response to fasting for 48 h. In contrast, sucrose-supplementation resulted in a significant increase in this pathway in both adipose tissue depots. Glyceroneogenesis was higher in mesenteric adipose tissue as compared with epididymal adipose tissue in all groups; however, a statistically significant difference was only observed in the sucrose-supplemented group (Table 2).
... 48-h fast caused a significantly lower incorporation of total glucose carbon into triglyceride glycerol as compared with controls. In contrast, sucrose supplementation resulted in a higher total contribution of glucose carbon to triglyceride glycerol (Table 2). The direct contribution of glucose to triglyceride glycerol was ∼80 nmol/g/h in control animals in both adipose depots (Table 2). In the 48-h-fasted animals the direct contribution of glucose via glycolysis was negligible. In contrast, sucrose supplementation resulted in a doubling of the direct contribution of glucose to triglyceride glycerol in both adipose tissue depots.
We confirmed the predominance of glyceroneogenesis, as compared with glycolysis,.... We examined the mesenteric adipose tissue of sucrose supplemented rats because glyceroneogenesis was highest in the adipose tissue of this group. ... [the results show] ... a greater contribution of glyceroneogenesis relative to the direct contribution of glucose via glycolysis to triglyceride glycerol synthesis (Fig. 3).
Fatty Acid Synthesis in Adipose Tissue: The incorporation of 14C of glucose into fatty acids was negligible in 48-h-fasted animals and high in controls in both the epididymal and mesenteric adipose tissue (Table 4). Furthermore, fatty acid synthesis in the sucrose-supplemented group was significantly higher as compared with control animals in both adipose tissue depots examined.
Note: epididymal and mesenteric adipose depots are types of visceral fat. Interesting, no? Glyceroneogenesis rates in the fat generally considered to be the more metabolically active are not changed by fasting vs. normal feeding. They increase in response to sucrose supplementation. So excess carbs caused an increase in G3P production from pyruvate/lactate. So much for the view of GlyNG as a minor alternative path. Sucrose did increase the absolute contribution from glycolysis, but the contribution of GlyNG was also stimulated. Again, it should be remembered that DNL is a more significant pathway for triglycerides in the rat. So those rats made fatty acids from the excess glucose, used some of the glucose to make G3P, but made the additional required to esterify the synthesized fatty acids predominantly from GlyNG.
My take-away message from this discussion is that the body gets the G3P it needs to esterify the fat it needs to store from the available substrates. Since humans use less glucose for DNL than rats, it is possible we use more to make G3P when it is "lying around", but GlyNG occurs at considerable rates continually, and is at the ready to "step up" when needed. The body has better uses for glucose apparently under normal conditions, and it has a ready supply of other substrates to make G3P in adipose tissue.
Glyceroneogenesis in the Skeletal Muscle: Our data are the first demonstration of glyceroneogenesis in skeletal muscles. In response to fasting as well as sucrose feeding, glyceroneogenesis was the main contributor to triglyceride glycerol formation, whereas the direct contribution of glucose was not measurable. .... Although we anticipated that glyceroneogenesis would be a functional pathway, due to the presence of PEPCK-C activity in skeletal muscle (14), the dominance of this pathway was unexpected. Even more surprising was the lack of a direct contribution of glucose to G-3-P synthesis, given that in response to a glucose load, skeletal muscle is responsible for the majority (∼85%) of insulin-mediated glucose uptake (62). Our data demonstrating a marginal contribution of glucose to triglyceride glycerol in skeletal muscle are consistent with the report of Guo and Jensen (15)...
Hepatic (Liver) Glyceroneogenesis: The fractional contribution of gluconeogenesis to the glucose Ra changed as expected (about 30% lower in controls, which increased to ∼60% after a 48-h fast), whereas glyceroneogenesis remained constant at about ∼60% under all conditions studied. Furthermore, glyceroneogenesis, and not glucose metabolism via glycolysis, was the dominant pathway for hepatic triglyceride glycerol synthesis, even in sucrose-fed, glucose-infused animals. ...
The above are pretty self-explanatory.
I saved the opening paragraph of the discussion for last, as it summarizes the above nicely:
In the present study we have examined the relative contribution of glyceroneogenesis and glucose via glycolysis to triglyceride glycerol synthesis in the rat. Our data show that glyceroneogenesis is quantitatively the predominant pathway for triglyceride glycerol synthesis in white adipose tissue, skeletal muscle, and liver during extended fasting as well as during periods of glucose availability. Surprisingly, the highest rates of glyceroneogenesis in adipose tissue were observed in sucrose-supplemented animals, when fatty acid synthesis and triglyceride deposition were high.
The *surprising* high rates of glyceroneogenesis under lipogenic conditions - e.g. conditions under which the rats were making fatty acids - are consistent with what is expected to go on in a low-carb, high-fat fed state. Only now the source of fatty acids is directly from the diet ("deposited" by chylos). There is no reason to believe that GlyNG wouldn't be increased in response to the *need* to store those fatty acids.
In conclusion the authors outline where the understanding of GlyNG regulation remains unresolved.
(Note: I'll address the epinepherine part at some future date)
Last, but not least, I would be remiss if I didn't address the date and source of this paper. It was submitted in June of 2008 and first published in July 2008. This was after the initial release of GCBC, but Hanson (a co-author) has been identified by Taubes as having vetted his version of G3P in the book to ensure its accuracy. GCBC was released relatively late in 2007 (September). This current article was rather detailed and embodied a considerable amount of research. Given the amount of work that would have gone into writing up the material, it is reasonable to assume that the research itself was mostly complete if not concluded months prior - e.g. though not compiled, no researcher ignores the results as they record data! Most of the work may well have been completed in advance of Hanson's review of GCBC. In other words, it seems unlikely that Hanson's view on the role of G3P and glyceroneogenesis was altered considerably from before the publication of GCBC to after as Taubes implies. That the latest work wasn't published formally until 2008 is not evidence of some great sea change in the understanding of the role of GlyNG in esterification. There's no evidence that this work did anything more than strengthen the mounting evidence of GlyNG's importance as a metabolic pathway (as summarized in the 2002 & 2003 papers). I'm still left most befuddled by this aspect of the controversy. At the very least, I think it was incumbent upon Taubes to follow this up instead of repeating his G3P theory in lecture after lecture as if it were established fact.