Designed By Nature

A paradigm shift in understanding

I’ve looked into various topics related to metabolism and what a high fat diet changes versus high carb. Topics such as heat production, weight management, ATP production, protein sparing, lactate, BHB, glycogen, starvation, evolution, bone health and collagen cross-links specifically, pyruvate etc.. have come together in a meaningful way.

What is presented below is a paradigm shift in my understanding of why the things are the way they are and at the center we find the evolutionary implementation of heat production.

When we acquired the trait I don’t know, but we certainly do posses the ability to increase our body heat production. It is possible this is a feature that developed when the first forms of multicellular life was challenged by snowball earth or maybe it came in later.

Heat production to survive cold is, needless to say, essential.  I’ve already argued before (see references at the bottom) that the main purpose of body fat isn’t primarily to survive starvation in winter periods.  It does help of course but it doesn’t work in cold climates.  Do not eat for a few days and your body heat drops noticeably.  Cold can kill you overnight with hands and feet the first to freeze.  Not ideal to survive.

So what does it take to increase heat production? What are the consequences?

Chronic higher fat availability (circulating in our body) seems to be required to sustain a higher heat production capacity.

• Your body needs sufficient access to fat, continuously.

On a per gram basis, because fat has 9 calories, it can produce double the amount of heat.

Using fat for heat production poses two problems though:

1. Producing more heat is an extra energy consumer
2. Chemically an increase in heat can cause more undesired reactions

1) If heat production is so important for survival then it requires serious energy optimization to cover the timeframe of cold exposure.  This can be done by lowering ATP requirements. 

This is actually being done. When the body shifts energy metabolism almost fully to fatty acids, ATP production is reduced where possible. The brain is exempt from this as it has a very limited supply of fatty acids that it can work with.

Brown fat, which is the source of the increase in heat production, becomes very active yet does not produce a lot of ATP because the energy is being wasted towards heat.

When a cell reduces its ATP production to save energy for heat production, it has to inhibit growth.  We see that AMPK inhibits mTOR, mTOR doesn’t inhibit AMPK! This naturally reduces the amino acid requirements.

2) But why fat?  Why not also use glucose to lose some electrons and generate heat?  Why did evolution decide on fat?

The greater energy density per gram is already a major advantage but when the heat is increased, using glucose becomes increasingly a problem due to glycation (the Maillard reaction).

Glucose binds to protein and fatty acids. This renders protein unusable and together with the modified lipids it creates advanced glycation end products (AGEs).

Chemically it seems necessary to reduce circulating glucose in our bodies. Damaged protein would require building new ones but we’re in a situation where we cannot spend ATP on it.

Evolution seems to have sorted out this situation long time ago. If heat needs to be produced:

• circulating glucose must go down
• fat must be used for heat production

This is why we also see a reduction in pyruvate. It means that less amino acids are used for glucose production while favoring glycerol. This way glucose availability remains low and we can avoid protein breakdown.

The lower we can keep glucose, the more heat we can generate but this has put evolution in front of an other problem to solve.

2 problems solved, 1 created

With ATP production reduced and glucose levels suppressed, the cells within the body risk falling short on ATP. A monitoring and signaling system is required and so evolution evolved providing a solution.

This is where cytosolic glycogen comes in.  When cellular glycogen levels decline, more cytosolic glycolysis takes place generating more lactate.  This increases BHB influx into the cell to support ATP production. 

Cellular glycogen works as a measurement of sufficient ATP production.  Sufficient extracellular substrate maintains glycogen levels, insufficient makes them decline. This is also why hypoxia directly stimulates lactate production. It immediately threatens mitochondrial ATP production.

Increased lactate will also stimulate more mitochondrial biogenesis so that more ATP can be produced through oxidation in the mitochondria rather than cytosolic glycolysis. 

Mitochondria therefor not exist to maximize ATP production, rather they exist to support a minimal level of mitochondrial ATP production.

In summary

• To produce extra heat the body must divert the energy from growth towards heat production.
• This can only be done if damage to protein (and lipids) is reduced
• Damage can be minimized when glucose is reduced
• Reducing glucose makes fat the only viable choice
• Low ATP is risky so a fail-safe mechanism is developed with beta-hydroxybutyrate as the fuel to resolve low availability

Related publications

• Bone health on a ketogenic diet
• The intimate triad glycogen – lactate – beta-hydroxybutyrate
• Metabolism on a ketogenic diet
• Cold on the outside – Warm on the inside

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