High Leucine Diets Stimulate Cerebral Branched-Chain Amino Acid Degradation and Modify Serotonin and Ketone Body Concentrations in a Pig Model

Abstract

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.

Standardized ileal digestible (SID) isoleucine requirement of barrows (15- to 30- kg) fed low crude protein diets

“…A BCAA imbalance may result in negative responses on ADFI, but most of it is associated with Leu excess in the diet, as shown for Val deficiency in diets containing Leu excess (GLAGUEN et al, 2012). More recently, Wessels et al (2016) corroborated the aforementioned finding, reporting that high levels of Leu in the liver can stimulate the BCKDH complex that catalyzes the irreversible degradation of all BCAAs, including valine (Val) and Ile. The result for ADFI (P>0.05) agrees with this explanation, since no effects were observed for increased SID Ile and because the SID Leu level was low in the experimental diets, due to the reduced CP content and not using spray dried blood cells.…”

Changes in tissue abundance and activity of enzymes related to branched-chain amino acid catabolism in dairy cows during early lactation

“…The absorbance at 340 nm and 30°C was recorded for 5 min to establish a baseline and the reaction was initiated with 20 µL of 10 mM α-ketoisovalerate (final concentration 1 mM) as substrate prewarmed to 30°C. In contrast to Nakai et al (2000), the assay buffer was prepared without exogenous dihydrolipoamide dehydrogenase, as validated by Wessels et al (2016). A control sample (bovine liver) with comparable BCKDH activity was included on each plate for inter-run calibration (accepted interassay CV <15%, intra-assay CV <5%) and sample data were normalized to the control.…”

Novel metabolic and physiological functions of branched chain amino acids: a review

“…Similarly, another experiment in finishing pigs reported that leucine addition increased juiciness accompanying the increase in intramuscular fat content occurring with a protein deficient diet [53]. However, supplementation of excess leucine (3.75%) in the diet changes plasma amino acid-derived metabolites, which may limit the use of high Leu diets to treat muscle atrophy [54]. Therefore, a high dose of leucine could be toxic and finding a suitable supplementation level of leucine is vital for future use.…”