Do ketones from HVMN Ketone get turned back into fat?

Authored by Justin Liau • 
January 18, 2018
 • 2 min read

Metabolism is highly complex and there are many factors that affect fuel use. There are also big differences between all of the tissues in the body (fat vs liver vs muscle vs brain vs heart). Important factors in fuel use include uptake into tissues, enzyme activity and end product inhibition (i.e The Randle Cycle). Just because there is an enzyme pathway that could conceivably make a conversion does not mean it is operational in human metabolism. 

Ketone metabolism evolved to provide a simple and rapidly metabolized fuel source that would spare the use of carbs, protein and also they regulate their own production by slowing down fat release. There are very few steps involved in ketone breakdown compared to fat (beta oxidation) and glucose (glycolysis). Also there is no hormonal regulation or transport regulation of ketones into the cell or mitochondria. This means that, when present ketones are used in preference to other fuels and exert an inhibitory effect on the use of other fuels. 

There is not a metabolic pathway whereby ketones are easily turned back into fat.

The process of making new fat is called de novo lipogenesis (DNL). This mainly happens in the cytosol of liver and the adipose (fat) tissue. Evidence for DNL happening elsewhere in the body is limited. 

Note that the pathway for fat breakdown (beta oxidation) takes place in the mitochondria and uses a different series of enzymes, so just elevating the acetyl CoA (ACoA) inside the mitochondria will not trigger fat synthesis. 

Ketones can only be converted to ACoA inside the mitochondria. 

The liver cannot convert ketones into ACoA as it doesn’t have succinyl CoA thiolase enzyme. Therefore BHB is highly unlikely to contribute to DNL in the liver. 

There are two types of fat tissue: white (stores lipid) and brown (responsible for thermogenesis: making heat). White adipose tissue does not highly express the transporter for ketones (MCT) so is unlikely to be a major site of ketone uptake. In any case, if ketones were taken up by white adipose tissue, it has been shown that only a small amount of fat stores come from DNL (~10%), and only when the body is in energy excess. Therefore conversion of ketones back into fat would likely be minor, if it occurred at all. 

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