Short-Chain Fatty Acids in the Metabolism of Heart Failure – Rethinking the Fat Stigma

Figures

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  Figure 1. Production, distribution and yield of short-chain fatty acids (SCFAs) in different tissues. After consumption, undigested fiber reaches the colon and is fermented by microbiota. The product of this process are SCFAs. Via the portal vein SCFAs are transported to the liver and then systemically distributed. (A) Utilization of SCFAs in the colon: Butyrate is an important energy source for colonocytes. (B) Utilization of SCFAs in the liver: Propionate is mostly metabolized in the liver. (C) Relative concentrations of SCFAs in peripheral blood: Acetate has the highest peripheral concentrations. This is followed by propionate, while butyrate shows the lowest peripheral concentrations (43). Created with BioRender.com.

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  Figure 2. Cellular fatty acid transport depending on chain length and changes in HF. (A) In healthy myocardium: Long-chain fatty acids (LCFAs) enter the cell via fatty acid translocase (FAT/CD36) and the mitochondrion via the carnitine shuttle (CPT1, 2). Medium-chain fatty acids (MCFAs) enter the cell via monocarboxylate transporter 1 (MCT1) and the mitochondrion via CPT1, 2 or transporter independent. Short-chain fatty acids (SCFAs) enter the cell via monocarboxylate transporter 1 (MCT1) or through transporter-independent mechanisms. Passage across the mitochondrial membrane is as well-transporter-independent. Inside the mitochondrion both LCFAs, MCFAs and SCFAs are processed through beta-oxidation and the TCA cycle for ATP-generation. (B) In diseased myocardium: LCFA uptake into the cell and mitochondrion is decreased at least in part because the expression of FAT/CD36 and CPT1, 2 are diminished. On the other hand, SCFA uptake into the cell as well as the mitochondrion is increased, but this is not sufficient to prevent a reduction in ATP production. Changes in MCFA oxidation are not well-described. Created with BioRender.com.