King Grub
2016-05-18, 08:22
In addition to its role as an essential protein component, leucine (Leu) displays several other metabolic functions such as activation of protein synthesis. This property makes it an interesting amino acid for the therapy of human muscle atrophy and for livestock production. However, Leu can stimulate its own degradation via the branched-chain keto acid dehydrogenase complex (BCKDH). To examine the response of several tissues to excessive Leu, pigs were fed diets containing two- (L2) and four-fold (L4) higher Leu contents than the recommended amount (control). We found that the L4 diet led to a pronounced increase in BCKDH activity in the brain (2.5-fold, P < 0.05), liver (1.8-fold, P < 0.05) and cardiac muscle (1.7-fold, P < 0.05), whereas we found no changes in enzyme activity in the pancreas, skeletal muscle, adipose tissue and intestinal mucosa. The L2 diet had only weak effects on BCKDH activity. Both high Leu diets reduced the concentrations of free valine and isoleucine in nearly all tissues. In the brain, high Leu diets modified the amount of tryptophan available: for serotonin synthesis. Compared to the controls, pigs treated with the high Leu diets consumed less food, showed increased plasma concentrations of 3-hydroxybutyrate and reduced levels of circulating serotonin. In conclusion, excessive Leu can stimulate BCKDH activity in several tissues, including the brain. Changes in cerebral tryptophan, along with the changes in amino acid-derived metabolites in the plasma may limit the use of high Leu diets to treat muscle atrophy or to increase muscle growth.
The current study sought to elucidate tissue-specific responses of BCKDH activity and amino acid derived metabolites in response to diets that contained 2- and 4-fold higher Leu amounts than required. We showed that pigs fed high Leu diets had lower food intake, which may explain the decline in growth observed in these animals. We further observed an increase in BCKDH activity in all tissues except the skeletal muscle and adipose tissue in response to high Leu diets. Interestingly, the highest increase in BCKDH activity in response to excessive Leu consumption was observed in the brain. The stimulated BCKDH activity and increased Leu concentration in the brain of pigs fed the high Leu diets provide evidence for elevated transport of Leu across the blood-brain barrier. Because excessive Leu in the brain is associated with neurological dysfunction, the observed rise in cerebral BCKDH activity is presumably a protective mechanism against Leu-associated neuronal disorders.
BCAAs and aromatic amino acids such as Trp share the same brain transporters. Thus, we hypothesized that cerebral Trp concentration declines in response to excessive Leu consumption. Because BCAAs include not only Leu but also Ile and Val, we analyzed all three BCAAs and observed that pigs fed the high Leu diets had increased plasma concentrations of Leu but reduced concentrations of Ile and Val. The reduction of Ile and Val in response to high Leu-diets is a well-described phenomenon and is caused by the stimulated BCKDH activity, which in turn degrades not only Leu but also Ile and Val.
In conclusion, excessive Leu intake can stimulate BCKDH activity in several tissues, including the brain. The changes in cerebral Trp, along with the alterations of plasma amino acid-derived metabolites such as serotonin and 3-hydroxybutyrate may limit the use of high Leu diets to treat muscle atrophy. The current findings may also be relevant to the fact that BCAAs comprise 20–40% of dietary proteins and that protein is excessively consumed in industrialized countries
High Leucine Diets Stimulate Cerebral Branched-Chain Amino Acid Degradation and Modify Serotonin and Ketone Body Concentrations in a Pig Model. PLOS One, March 1 2016.
The current study sought to elucidate tissue-specific responses of BCKDH activity and amino acid derived metabolites in response to diets that contained 2- and 4-fold higher Leu amounts than required. We showed that pigs fed high Leu diets had lower food intake, which may explain the decline in growth observed in these animals. We further observed an increase in BCKDH activity in all tissues except the skeletal muscle and adipose tissue in response to high Leu diets. Interestingly, the highest increase in BCKDH activity in response to excessive Leu consumption was observed in the brain. The stimulated BCKDH activity and increased Leu concentration in the brain of pigs fed the high Leu diets provide evidence for elevated transport of Leu across the blood-brain barrier. Because excessive Leu in the brain is associated with neurological dysfunction, the observed rise in cerebral BCKDH activity is presumably a protective mechanism against Leu-associated neuronal disorders.
BCAAs and aromatic amino acids such as Trp share the same brain transporters. Thus, we hypothesized that cerebral Trp concentration declines in response to excessive Leu consumption. Because BCAAs include not only Leu but also Ile and Val, we analyzed all three BCAAs and observed that pigs fed the high Leu diets had increased plasma concentrations of Leu but reduced concentrations of Ile and Val. The reduction of Ile and Val in response to high Leu-diets is a well-described phenomenon and is caused by the stimulated BCKDH activity, which in turn degrades not only Leu but also Ile and Val.
In conclusion, excessive Leu intake can stimulate BCKDH activity in several tissues, including the brain. The changes in cerebral Trp, along with the alterations of plasma amino acid-derived metabolites such as serotonin and 3-hydroxybutyrate may limit the use of high Leu diets to treat muscle atrophy. The current findings may also be relevant to the fact that BCAAs comprise 20–40% of dietary proteins and that protein is excessively consumed in industrialized countries
High Leucine Diets Stimulate Cerebral Branched-Chain Amino Acid Degradation and Modify Serotonin and Ketone Body Concentrations in a Pig Model. PLOS One, March 1 2016.