20/11/2022
Figure Key: Schematic diagram depicting the conflicting role of branched chain amino acids (BCAAs) in liver diseases.
The left (red) side represents a summary of known molecular pathways in the liver and gut microbiota dysbiosis upon elevated circulatory BCAAs that may contribute to the progression of liver diseases.
The right (green) side summarizes the potential mechanisms that may explain how BCAA supplementation improves liver diseases’ outcomes.
(1) Ingested BCAA undergoes transamination with α-ketoglutarate by BCATs, which generates glutamate, which is used in ammonia detoxification to glutamine.
(2) Elevated BCAAs upregulate PPARα, which suppressed the rate-limiting enzyme of BCAAs’ catabolism, BCKDK.
(3) Enhanced BC-acyl-CoA due to the lower suppression of BCKDH.
(4) Supplementation increases beneficial gut microbiota while suppressing the phylum proteobacteria that includes pathogenic genera.
Abbreviations: BCAAs, branched-chain amino acids; AA, amino acid; BCATs, branched-chain amino transferases; BCKAs, branched-chain α-ketoacids; BCKDH, branched-chain alpha-keto acid dehydrogenase; BCKDK, BCKDH kinase; IRS-1, insulin receptor substrate 1; NAFLD, non-alcoholic fatty liver diseases; GLU, glutamate; GLN, glutamine; HCC, hepatocellular carcinoma; PI3K/AkT, phosphatidylinositol 3-kinase/protein kinase B; PPAR-α, peroxisome proliferator-activated receptor alpha; mTORC1, mTOR complex 1; BC-acyl CoAs, branched-chain acyl-CoAs; TGF-β1, transforming growth factor beta 1; VEGF, vascular endothelial growth factor.
Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220261/
