Thursday, February 11, 2010

Glycero and Gluco Neogenesis: Related but Not Twins

I recently became aware of a blog posting by Dr. James Carlson that was inspired by my article Is the Fable of Unfettered Fat Burning Derailing Your Low Carb Diet?.  Dr. Carlson was asked by a Facebook follower to read the article and to elaborate on the "mechanism where your body can accumulate or at least not lose fat because of dietary protein intake".  I'm assuming the mechanism she is referring to is the biochemical pathway glyceroneogenesis which can use amino acids from dietary protein to synthesize the glycerol backbone necessary for triglyceride formation.  You can read Dr. Carlson's response here.  Although I may be mistaken, it seems Dr. Carlson is stating that glyceroneogenesis is simply gluconeogenesis with an additional step at the end.  Because that is not what glyceroneogenesis is and because my article was the impetus for the discussion, I feel the need to clarify.

Most people who follow low carb diets know what gluconeogenesis is: the creation of glucose from non-carbohydrate sources like lactate, glycerol, and glucogenic amino acids. Certain cells in the human body can only utilize glucose for fuel and gluconeogenesis is the process the body uses to make glucose when very little carbohydrate is coming in via one's diet. Gluconeogenesis takes place primarily in the liver and the resulting glucose is released into the bloodstream where it travels to the cells that need it. Again, I could be wrong, but it appears Dr. Carlson is stating that glyceroneogenesis  =  gluconeogenesis in the liver  +  glycerol 3-phosphate formation via glycolysis in fat cells. In other words, he believes glyceroneogenesis occurs when glucose formed in the liver from lactate, glycerol, or amino acids is taken up by fat cells and transformed into glycerol 3-phosphate, the glycerol backbone of a triglyceride molecule. Theoretically, this could happen but this process is not glyceroneogenesis. Glyceroneogenesis occurs in the fat cells themselves - no liver required. Glucogenic amino acids (or lactate) are taken up directly by fat cells and transformed into glycerol 3-phosphate by what would best be described as a truncated version of gluconeogenesis:

Although both (gluconeogenesis + glycolysis) and glyceroneogenesis can potentially provide the glycerol 3-phosphate necessary for triglyceride synthesis (aka body fat accumulation) on a low carb diet, I find glyceroneogenesis the more compelling candidate.  In general, only the amount of glucose needed for those cells that require it will be produced by gluconeogenesis.  And that requirement is not very much - I've seen references for as little as 40 grams of glucose per day during prolonged fasting or very low carb intake.  This glucose is consumed only by those cells that need it so that there is no "extra" for fat cells to use to make glycerol 3-phosphate.  Also, glycerol 3-phosphate synthesis from glucose occurs via glycolysis, and glycolysis is greatly reduced in fat cells during low carb intake.  Unlike glycolysis, glyceroneogenesis is up-regulated in fat cells during low carb intake.  The only major barrier to glyceroneogenesis when insulin is low is lack of substrate, but since many low carb dieters eat a good amount of protein, this scenario won't necessarily happen without conscious intervention.

Does this mean that reducing dietary protein is a good strategy for encouraging fat loss on a reduced carbohydrate diet?  In my opinion, it could work, but should only be attempted if fat loss has stalled for an appreciable amount of time or if one is gaining body fat.  Reducing protein intake is tricky - it has the potential to cause a loss of muscle mass which is something most of us don't want.  A good idea would be to calculate your individual protein need to see where you stand.  If you find that you are eating more protein than you need and you are not experiencing much in the way of fat loss success on a low carb diet, try reducing your protein intake a bit (or maybe more than a bit depending on how much you're eating).  Your body may be a pro-glyceroneogenesis machine and delivering less amino acid substrate to your fat cells may just do the trick.

Note:  the biochemical pathway diagrams in this article are technically correct but not complete.  In other words, I hope they help you understand the article but if you want to pass a biochemistry exam, don't study these diagrams or you will surely fail!  ;)