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Accelerated lysine metabolism conveys kidney protection in salt-sensitive hypertension

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Accelerated lysine metabolism conveys kidney protection in salt-sensitive hypertension. / Rinschen, Markus M; Palygin, Oleg; El-Meanawy, Ashraf; Domingo-Almenara, Xavier; Palermo, Amelia; Dissanayake, Lashodya V; Golosova, Daria; Schafroth, Michael A; Guijas, Carlos; Demir, Fatih; Jaegers, Johannes; Gliozzi, Megan L; Xue, Jingchuan; Hoehne, Martin; Benzing, Thomas; Kok, Bernard P; Saez, Enrique; Bleich, Markus; Himmerkus, Nina; Weisz, Ora A; Cravatt, Benjamin F; Krüger, Marcus; Benton, H Paul; Siuzdak, Gary; Staruschenko, Alexander.

In: NAT COMMUN, Vol. 13, No. 1, 4099, 14.07.2022.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Rinschen, MM, Palygin, O, El-Meanawy, A, Domingo-Almenara, X, Palermo, A, Dissanayake, LV, Golosova, D, Schafroth, MA, Guijas, C, Demir, F, Jaegers, J, Gliozzi, ML, Xue, J, Hoehne, M, Benzing, T, Kok, BP, Saez, E, Bleich, M, Himmerkus, N, Weisz, OA, Cravatt, BF, Krüger, M, Benton, HP, Siuzdak, G & Staruschenko, A 2022, 'Accelerated lysine metabolism conveys kidney protection in salt-sensitive hypertension', NAT COMMUN, vol. 13, no. 1, 4099. https://doi.org/10.1038/s41467-022-31670-0

APA

Rinschen, M. M., Palygin, O., El-Meanawy, A., Domingo-Almenara, X., Palermo, A., Dissanayake, L. V., Golosova, D., Schafroth, M. A., Guijas, C., Demir, F., Jaegers, J., Gliozzi, M. L., Xue, J., Hoehne, M., Benzing, T., Kok, B. P., Saez, E., Bleich, M., Himmerkus, N., ... Staruschenko, A. (2022). Accelerated lysine metabolism conveys kidney protection in salt-sensitive hypertension. NAT COMMUN, 13(1), [4099]. https://doi.org/10.1038/s41467-022-31670-0

Vancouver

Rinschen MM, Palygin O, El-Meanawy A, Domingo-Almenara X, Palermo A, Dissanayake LV et al. Accelerated lysine metabolism conveys kidney protection in salt-sensitive hypertension. NAT COMMUN. 2022 Jul 14;13(1). 4099. https://doi.org/10.1038/s41467-022-31670-0

Bibtex

@article{1be9cf82076940cf91906b2761557125,
title = "Accelerated lysine metabolism conveys kidney protection in salt-sensitive hypertension",
abstract = "Hypertension and kidney disease have been repeatedly associated with genomic variants and alterations of lysine metabolism. Here, we combined stable isotope labeling with untargeted metabolomics to investigate lysine's metabolic fate in vivo. Dietary 13C6 labeled lysine was tracked to lysine metabolites across various organs. Globally, lysine reacts rapidly with molecules of the central carbon metabolism, but incorporates slowly into proteins and acylcarnitines. Lysine metabolism is accelerated in a rat model of hypertension and kidney damage, chiefly through N-alpha-mediated degradation. Lysine administration diminished development of hypertension and kidney injury. Protective mechanisms include diuresis, further acceleration of lysine conjugate formation, and inhibition of tubular albumin uptake. Lysine also conjugates with malonyl-CoA to form a novel metabolite Nε-malonyl-lysine to deplete malonyl-CoA from fatty acid synthesis. Through conjugate formation and excretion as fructoselysine, saccharopine, and Nε-acetyllysine, lysine lead to depletion of central carbon metabolites from the organism and kidney. Consistently, lysine administration to patients at risk for hypertension and kidney disease inhibited tubular albumin uptake, increased lysine conjugate formation, and reduced tricarboxylic acid (TCA) cycle metabolites, compared to kidney-healthy volunteers. In conclusion, lysine isotope tracing mapped an accelerated metabolism in hypertension, and lysine administration could protect kidneys in hypertensive kidney disease.",
keywords = "Albumins/metabolism, Animals, Carbon/metabolism, Humans, Hypertension/metabolism, Kidney/metabolism, Lysine/metabolism, Malonyl Coenzyme A/metabolism, Rats",
author = "Rinschen, {Markus M} and Oleg Palygin and Ashraf El-Meanawy and Xavier Domingo-Almenara and Amelia Palermo and Dissanayake, {Lashodya V} and Daria Golosova and Schafroth, {Michael A} and Carlos Guijas and Fatih Demir and Johannes Jaegers and Gliozzi, {Megan L} and Jingchuan Xue and Martin Hoehne and Thomas Benzing and Kok, {Bernard P} and Enrique Saez and Markus Bleich and Nina Himmerkus and Weisz, {Ora A} and Cravatt, {Benjamin F} and Marcus Kr{\"u}ger and Benton, {H Paul} and Gary Siuzdak and Alexander Staruschenko",
note = "{\textcopyright} 2022. The Author(s).",
year = "2022",
month = jul,
day = "14",
doi = "10.1038/s41467-022-31670-0",
language = "English",
volume = "13",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Accelerated lysine metabolism conveys kidney protection in salt-sensitive hypertension

AU - Rinschen, Markus M

AU - Palygin, Oleg

AU - El-Meanawy, Ashraf

AU - Domingo-Almenara, Xavier

AU - Palermo, Amelia

AU - Dissanayake, Lashodya V

AU - Golosova, Daria

AU - Schafroth, Michael A

AU - Guijas, Carlos

AU - Demir, Fatih

AU - Jaegers, Johannes

AU - Gliozzi, Megan L

AU - Xue, Jingchuan

AU - Hoehne, Martin

AU - Benzing, Thomas

AU - Kok, Bernard P

AU - Saez, Enrique

AU - Bleich, Markus

AU - Himmerkus, Nina

AU - Weisz, Ora A

AU - Cravatt, Benjamin F

AU - Krüger, Marcus

AU - Benton, H Paul

AU - Siuzdak, Gary

AU - Staruschenko, Alexander

N1 - © 2022. The Author(s).

PY - 2022/7/14

Y1 - 2022/7/14

N2 - Hypertension and kidney disease have been repeatedly associated with genomic variants and alterations of lysine metabolism. Here, we combined stable isotope labeling with untargeted metabolomics to investigate lysine's metabolic fate in vivo. Dietary 13C6 labeled lysine was tracked to lysine metabolites across various organs. Globally, lysine reacts rapidly with molecules of the central carbon metabolism, but incorporates slowly into proteins and acylcarnitines. Lysine metabolism is accelerated in a rat model of hypertension and kidney damage, chiefly through N-alpha-mediated degradation. Lysine administration diminished development of hypertension and kidney injury. Protective mechanisms include diuresis, further acceleration of lysine conjugate formation, and inhibition of tubular albumin uptake. Lysine also conjugates with malonyl-CoA to form a novel metabolite Nε-malonyl-lysine to deplete malonyl-CoA from fatty acid synthesis. Through conjugate formation and excretion as fructoselysine, saccharopine, and Nε-acetyllysine, lysine lead to depletion of central carbon metabolites from the organism and kidney. Consistently, lysine administration to patients at risk for hypertension and kidney disease inhibited tubular albumin uptake, increased lysine conjugate formation, and reduced tricarboxylic acid (TCA) cycle metabolites, compared to kidney-healthy volunteers. In conclusion, lysine isotope tracing mapped an accelerated metabolism in hypertension, and lysine administration could protect kidneys in hypertensive kidney disease.

AB - Hypertension and kidney disease have been repeatedly associated with genomic variants and alterations of lysine metabolism. Here, we combined stable isotope labeling with untargeted metabolomics to investigate lysine's metabolic fate in vivo. Dietary 13C6 labeled lysine was tracked to lysine metabolites across various organs. Globally, lysine reacts rapidly with molecules of the central carbon metabolism, but incorporates slowly into proteins and acylcarnitines. Lysine metabolism is accelerated in a rat model of hypertension and kidney damage, chiefly through N-alpha-mediated degradation. Lysine administration diminished development of hypertension and kidney injury. Protective mechanisms include diuresis, further acceleration of lysine conjugate formation, and inhibition of tubular albumin uptake. Lysine also conjugates with malonyl-CoA to form a novel metabolite Nε-malonyl-lysine to deplete malonyl-CoA from fatty acid synthesis. Through conjugate formation and excretion as fructoselysine, saccharopine, and Nε-acetyllysine, lysine lead to depletion of central carbon metabolites from the organism and kidney. Consistently, lysine administration to patients at risk for hypertension and kidney disease inhibited tubular albumin uptake, increased lysine conjugate formation, and reduced tricarboxylic acid (TCA) cycle metabolites, compared to kidney-healthy volunteers. In conclusion, lysine isotope tracing mapped an accelerated metabolism in hypertension, and lysine administration could protect kidneys in hypertensive kidney disease.

KW - Albumins/metabolism

KW - Animals

KW - Carbon/metabolism

KW - Humans

KW - Hypertension/metabolism

KW - Kidney/metabolism

KW - Lysine/metabolism

KW - Malonyl Coenzyme A/metabolism

KW - Rats

U2 - 10.1038/s41467-022-31670-0

DO - 10.1038/s41467-022-31670-0

M3 - SCORING: Journal article

C2 - 35835746

VL - 13

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

M1 - 4099

ER -