The Fatty Acid–Ketone Switch

In failing hearts, cardiomyocytes change their fuel preference.

By | June 1, 2016

Healthy cardiomyocytes (left panel) mainly use fatty acids as their energy source. To produce ATP, fatty acids are first converted into acylcarnitines, which are converted back to fatty-acyl-CoA and enter the β-oxidation cycle inside mitochondria. The resulting acetyl-CoAs then enter the citric acid cycle. In a mouse model of heart failure and in failing human hearts (right panel), cardiomyocytes depend more on ketones for energy. The ketone βOHB enters the mitochondrion where the enzyme BDH1 converts it into acetoacetate, whose products serve as substrates for the citric acid cycle. Both mice and humans with heart failure experience increased serum levels of βOHB, but in human cells βOHB and acylcarnitine levels go down. In mice, heart failure reduces the abundance of proteins involved in fatty acid oxidation. Both alterations suggest ketones are preferred over fatty acids in failing hearts.

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Avatar of: Carlos Oliveira

Carlos Oliveira

Posts: 1

June 26, 2016

As a suggestion for research in chronic heart failure, researchers could study  the GOOD  SYNERGISTIC EFFECTS OF SUPPLEMENTATION WITH  LOW DOSES OF CARNITINE (or Acetyl L Carnitine - ALCAR) ASSOCIATED TO MEDIUM-CHAIN TRIGLYCERIDES (as extra virgin coconut oil) improving cells energy  : Article : CARNITINE SUPPLEMENTATION AND KETOGENESIS BY SMALL -FOR -DATE NEONATES ON MEDIUM - AND LONG -CHAIN FATTY ACID FORMULAE", published in the Journal Biology of Neonate , 2000 , authors Labadaridis J, we can read that : "CARNITINE  is a key molecule in energy production from various substrates. Although it is generally believed that it plays no role in the metabolism of medium-chain triglycerides, quite a few data exist to the contrary. In the present study we investigated the effect of carnitine on ketogenesis in small-for-date neonates fed formulae of equal caloric value and fat content that was predominantly long-chain triglycerides or medium-chain triglycerides (46% of total fat).According to our results there was a statistically significant interaction between CARNITINE and the chain length of the administered fat with respect to ketone production.Increased ketogenesis was only shown by the neonates receiving MEDIUM-CHAIN TRIGLYCERIDES AND CARNITINE. Our results provide further evidence for the involvement of carnitine in medium-chain triglyceride metabolism."

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