While busting my head with Guyton’s Medical Physiology, I was very focused on the fat metabolism chapter. I was trying to grasp upon all the concepts and chemical processes that occur when something caught my attention.
It was: “failure to synthesize fats from carbohydrates in the absence of insulin“. I remember that context matters, which is why I fully engaged into seeing what it is all about. Guyton was describing the situation of diabetes mellitus saying that if insulin is not available, glucose cannot enter into cells efficiently.
This means there is a shortage of Acetyl-CoA and NADPH, both of which are needed to lipogenesis. Also, since there is little glucose available, there will be less of α-glycerophosphate which is also needed to create triglycerides (lipogenesis).
We know that you do not have to be diabetic (T1D in most of the cases) to have lower levels of insulin in your circulation, as well as little to no glucose inside your cells. Just limit the amount of carbohydrates you consume and this process of lipogenesis will not occur. But what is lipogenesis?
If you worry about dangerously low glucose levels, you should not. Your body can create on its own the sufficient amounts of glucose it needs for certain structures that cannot use fat for energy, such as the kidney cells, the retina, and the red blood cell, just to name a few. See Ron Rosedale’s explanation.
Ok, so lipogenesis.
Whenever excess glucose is ingested and cannot be stored in the muscles and in the liver (as these tanks are full), it is converted into triglycerides which will be stored into the adipose tissue. Besides, whenever glycogen tanks are full and there is further consumption of nutrients, their fate is to be stored in the adipose tissues. Here’s a study that shows how fatty acids are repartitioned away from oxidation (beta-oxidation) toward esterification in both the liver and muscle as a response to a short-term adaptation to a high-carb diet.
Here’s how the process of lipogenesis begins:
1. Lipogenesis uses Acetyl-CoA and it takes place in the cytosol (intra-cellular fluid). Acetyl-CoA needs to be transported from the Mitochondrial Matrix into the cytosol through the Mitochondrial Membrane.
It cannot pass the membrane as Acetyl-CoA itself, which is why it reacts with Oxaloacetate to form citrate. Citrate is carried by Citrate Transporter outside the Mitochondrial Matrix into the cytosol.
2. An inverse reaction from the one inside the MM (Mitochondrial Matrix) occurs and Acetyl-CoA is regenerated along with Oxaloacetate. Oxaloacetate generates Malate which is carried by Malate Transporter back into the MM, where it will be turned to Oxaloacetate again. Then, Oxaloacetate along with Acetyl-CoA can begin repeating the same process. This system is called The Citrate Malate Shuttle System.
3. Back into the cytosol, Acetyl-CoA will undergo TAG (triglyceride) synthesis or lipogenesis as long as there is enough α-glycerophosphate and NADPH to support the synthesis, both of which come from glucose, either from the glycolitic pathway or from the pentose phosphate pathway.
Again, these reactions cannot take place in a system where glucose is scarce. Keto-adapted individuals or people who follow ketogenic nutrition plans are in this position and their bodies will not have the luxury to shunt glucose into the adipose tissue because gluconeogenesis (creation of glucose from fats and from proteins) will serve to deliver glucose to the structures that cannot function without it (RBC, kidney cell, etc).
To be noted that excess glucose and excess protein can turn the lipogenesis process on. Guyton says that when protein is over-consumed (more than can efficiently be used), the amino-acids will form Acetyl-CoA and undergo the processes described above.
Overfeeding under High-Carb Diets
I would also like to add that under high-carbohydrate nutrition plans (that most of the people follow), overfeeding with either of the nutrients will lead to accumulation of TAG (triglycerides):
Carbohydrates -> Lipogenesis-> TAG in adipose tissues
Proteins -> Deamination->….->Lipogenesis-> TAG in adipose tissues
Fats + Glycerol -> TAG in adipose tissues.
The key take-away is that: by reducing carbohydrates and by keeping protein intake moderate you will have removed the mechanisms that support lipogenesis.
Several folks from the keto community have reported on eating 3000-5000 kcals and not gaining weight. I’ve personally done it when starting eating high-fat-low-carb because I was consuming 2500-3500 kcals with little exercise compared to my previous moderate carb diet. I was just starting with ketosis and it took a short-while until my hunger and cravings have been reduced and then eliminated.
For 2-3 weeks I’ve been eating this way and I was losing weight. This can probably be tied up to the water loss as well, but I know that energy consumption and energy exchange is different in high-fat diets compared to normal carb diets.
Basically we were overfeeding with fat under ketogenic diets and did not gain weight. I’m really curios into discovering what happens with the excess calories coming from fat under high-fat diets. I have some suspicions that I’ve touched in the upcoming book (see the end of the post) and Peter Attia has some theories as well. It has to do with energy as heat, energy exchange between systems, as well as higher resting metabolic rate.
For now, let’s stick to limiting carbohydrates and enjoying the benefits. Let me know your thoughts in either of the comment sections below.
1. Guyton, C. & Hall, J. E. (2010). Medical Physiology. Saunders.
2. Stoker, S. (2006). General, Organic, and Biological Chemistry. Cengage-Learning.
3. Stephen Phinney and Jeff Volek – The Art and Science of Low Carbohydrate Living
Photos: here and here