Regulation of the plasma amino acid profile by leucine via the system L amino acid transporter

Zhen, Hongmin; Nakamura, Kōichi; Kitaura, Yasuyuki; Kadota, Yasuhiro; Ishikawa, Takuya; Kondo, Yûsuke; Xu, Min-Jun; Shimomura, Yoshiharu

doi:10.1080/09168451.2015.1060845

Cited by 9 publications

(12 citation statements)

References 27 publications

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“…The BCAA and aromatic AA including Tyr, Tryptophan (Trp), and Phe share the same AA transport system across the plasma membrane, known as system-L AA transporters (LAT). The LAT system is a Na+-independent AA transporter that mediates transport of other neutral AA, including several essential AA [13,35]. The role of LAT in the regulation of Leu-induced alterations in the plasma AA profile has been recently demonstrated in mice [13].…”

Section: Discussionmentioning

confidence: 99%

“…The LAT system is a Na+-independent AA transporter that mediates transport of other neutral AA, including several essential AA [13,35]. The role of LAT in the regulation of Leu-induced alterations in the plasma AA profile has been recently demonstrated in mice [13]. They found that the elevation of plasma Leu concentration lead to a decrease in the plasma concentrations of Ile, Val, Met, Phe, and Tyr; and that LAT is involved in the mechanism of Leu action.…”

Section: Discussionmentioning

confidence: 99%

“…This may suggest that there is a lag time in the action of Leu in reducing the plasma concentrations of BCAA and other AA. It is probable that the elevated cellular Leu concentration, but not that of plasma, is responsible for triggering other AA uptake into cells from the circulation through activation of AA transporters [13]. In the current study, it is also likely that interaction (competition) among AA for uptake has occurred after the bolus duodenal infusion of Leu, and that the reduction of several AA concentrations in the plasma might also be a consequence of less AA uptake in the small intestine that warrant further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Leucine has gained much attention as a potentially limiting AA for milk and milk protein yields in studies involving dairy cows [7–9]. Also, studies have shown that administration of BCAA (especially Leu) has a great impact on the plasma AA profiles in human [10,11], pig [12], and mice [13]. However, the physiological significance and the underlying molecular mechanisms responsible for the regulation of plasma AA profile after Leu administration are not yet well understood.…”

Section: Introductionmentioning

confidence: 99%

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Plasma amino acids and metabolic profiling of dairy cows in response to a bolus duodenal infusion of leucine

et al. 2017

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Leucine (Leu), one of the three branch chain amino acids, acts as a signaling molecule in the regulation of overall amino acid (AA) and protein metabolism. Leucine is also considered to be a potent stimulus for the secretion of insulin from pancreatice β-cells. Our objective was to study the effects of a duodenal bolus infusion of Leu on insulin and glucagon secretion, on plasma AA concentrations, and to do a metabolomic profiling of dairy cows as compared to infusions with either glucose or saline. Six duodenum-fistulated Holstein cows were studied in a replicated 3 × 3 Latin square design with 3 periods of 7 days, in which the treatments were applied at the end of each period. The treatments were duodenal bolus infusions of Leu (DIL; 0.15 g/kg body weight), glucose (DIG; at Leu equimolar dosage) or saline (SAL). On the day of infusion, the treatments were duodenally infused after 5 h of fasting. Blood samples were collected at -15, 0, 10, 20, 30, 40, 50, 60, 75, 90, 120, 180, 210, 240 and 300 min relative to the start of infusion. Blood plasma was assayed for concentrations of insulin, glucagon, glucose and AA. The metabolome was also characterized in selected plasma samples (i.e. from 0, 50, and 120 min relative to the infusion). Body weight, feed intake, milk yield and milk composition were recorded throughout the experiment. The Leu infusion resulted in significant increases of Leu in plasma reaching 20 and 15-fold greater values than that in DIG and SAL, respectively. The elevation of plasma Leu concentrations after the infusion led to a significant decrease (P<0.05) in the plasma concentrations of isoleucine, valine, glycine, and alanine. In addition, the mean concentrations of lysine, methionine, phenylalanine, proline, serine, taurine, threonine, and asparagine across all time-points in plasma of DIL cows were reduced (P<0.05) compared with the other groups. In contrast to the working hypothesis about an insulinotropic effect of Leu, the circulating concentrations of insulin were not affected by Leu. In DIG, insulin and glucose concentrations peaked at 30–40 and 40–50 min after the infusion, respectively. Insulin concentrations were greater (P<0.05) from 30–40 min in DIG than DIL and SAL, and glucose was elevated in DIG over DIL and SAL from 30–75 min and 40–50 min, respectively. Multivariate metabolomics data analysis (principal component analysis and partial least squares discriminant analysis) revealed a clear separation when the DIL cows were compared with the DIG and SAL cows at 50 and 120 min after the infusion. By using this analysis, several metabolites, mainly acylcarnitines, methionine sulfoxide and components from the kynurenine pathway were identified as the most relevant for separating the treatment groups. These results suggest that Leu regulates the plasma concentrations of branched-chain AA, and other AA, apparently by stimulating their influx into the cells from the circulation. A single-dose duodenal infusion of Leu did not elicit an apparent insulin response, but affected multiple inte...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Plasma amino acids and metabolic profiling of dairy cows in response to a bolus duodenal infusion of leucine

et al. 2017

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“…Imbalances between branched-chain amino acids have been reported by other authors to have undesirable metabolic effects in patients with PA and MMA (26). Also, excess Leu was found to reduce plasma Val and Ile by interfering with the LAT1 transport of amino acids (27). In addition, animals fed high doses of Leu show low central nervous system concentrations of tryptophan (Trp), Val, Ile, Met and low brain alanine (Ala), which might affect the synthesis of neurotransmitters (28).…”

Section: Discussionmentioning

confidence: 78%

Severe Anemia in Patients with Propionic Acidemia is Associated with Low Plasma Levels of Valine, Isoleucine and Methionine

Stanescu¹,

Bélanger-Quintana²,

Quintero³

et al. 2020

Preprint

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Background. Propionic acidemia (AP), an inborn error of metabolism, is caused by a deficiency in propionyl-CoA carboxylase. Patients have to follow a diet restricted in the propiogenic amino acids isoleucine (Iso), valine (Val), methionine (Met) and threonine (Thr); proper adherence can prevent and treat acute decompensation and increase life expectancy. However, chronic complications occur in several organs even though metabolic control may be largely maintained. Bone marrow aplasia and cytopenia are among the more common. Materials and methods. In this retrospective study, data for patients with PA being monitored at the Hospital Ramón y Cajal (Madrid, Spain) (n=10) were examined to statistically detect relationships between hematological complications outside of metabolic decompensation episodes, and plasma amino acids provided by the diet, urinary organic acids and plasma odd-chain fatty acids. High ferritin levels were deemed to indicate that a patient had received repeated transfusions for severe anemia since data on hemoglobin levels at the moment of transfusion were not always passed on by the attending centers. Results. Three patients had severe, persistent anemia that required repeated blood transfusions leading to high ferritin levels. Their low plasma Val, Ile and Met suggested that their anemia had a nutritional component. Conclusion. The present results suggest that severe anemia in patients with PA is associated with low plasma levels of Val, Ile and Met.

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mTORC1 is involved in the regulation of branched‐chain amino acid catabolism in mouse heart

et al. 2016

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The branched‐chain α‐ketoacid dehydrogenase ( BCKDH ) complex regulates branched‐chain amino acid ( BCAA ) catabolism by controlling the second step of this catabolic pathway. In the present study, we examined the in vivo effects of treatment with an mTORC 1 inhibitor, rapamycin, on cardiac BCKDH complex activity in mice. Oral administration of leucine in control mice significantly activated the cardiac BCKDH complex with an increase in cardiac concentrations of leucine and α‐ketoisocaproate. However, rapamycin treatment significantly suppressed the leucine‐induced activation of the complex despite similar increases in cardiac leucine and α‐ketoisocaproate levels. Rapamycin treatment fully inhibited mTORC 1 activity, measured by the phosphorylation state of ribosomal protein S6 kinase 1. These results suggest that mTORC 1 is involved in the regulation of cardiac BCAA catabolism.

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Regulation of the plasma amino acid profile by leucine via the system L amino acid transporter

Cited by 9 publications

References 27 publications

Plasma amino acids and metabolic profiling of dairy cows in response to a bolus duodenal infusion of leucine

Plasma amino acids and metabolic profiling of dairy cows in response to a bolus duodenal infusion of leucine

Severe Anemia in Patients with Propionic Acidemia is Associated with Low Plasma Levels of Valine, Isoleucine and Methionine

mTORC1 is involved in the regulation of branched‐chain amino acid catabolism in mouse heart

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