Neprilysin activity is increased in metabolic dysfunction-associated steatotic liver disease and normalizes after bariatric surgery or GLP-1 therapy

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

Standard

Neprilysin activity is increased in metabolic dysfunction-associated steatotic liver disease and normalizes after bariatric surgery or GLP-1 therapy. / Kjeldsen, Sasha A.S.; Gluud, Lise L.; Werge, Mikkel P.; Pedersen, Julie S.; Bendtsen, Flemming; Alexiadou, Kleopatra; Tan, Tricia; Torekov, Signe S.; Iepsen, Eva W.; Jensen, Nicole J.; Richter, Michael M.; Goetze, Jens P.; Rungby, Jørgen; Hartmann, Bolette; Holst, Jens J.; Holst, Birgitte; Holt, Joachim; Gustafsson, Finn; Madsbad, Sten; Svane, Maria S.; Bojsen-Møller, Kirstine N.; Wewer Albrechtsen, Nicolai J.

In: iScience, Vol. 26, No. 11, 108190, 2023.

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

Harvard

Kjeldsen, SAS, Gluud, LL, Werge, MP, Pedersen, JS, Bendtsen, F, Alexiadou, K, Tan, T, Torekov, SS, Iepsen, EW, Jensen, NJ, Richter, MM, Goetze, JP, Rungby, J, Hartmann, B, Holst, JJ, Holst, B, Holt, J, Gustafsson, F, Madsbad, S, Svane, MS, Bojsen-Møller, KN & Wewer Albrechtsen, NJ 2023, 'Neprilysin activity is increased in metabolic dysfunction-associated steatotic liver disease and normalizes after bariatric surgery or GLP-1 therapy', iScience, vol. 26, no. 11, 108190. https://doi.org/10.1016/j.isci.2023.108190

APA

Kjeldsen, S. A. S., Gluud, L. L., Werge, M. P., Pedersen, J. S., Bendtsen, F., Alexiadou, K., Tan, T., Torekov, S. S., Iepsen, E. W., Jensen, N. J., Richter, M. M., Goetze, J. P., Rungby, J., Hartmann, B., Holst, J. J., Holst, B., Holt, J., Gustafsson, F., Madsbad, S., ... Wewer Albrechtsen, N. J. (2023). Neprilysin activity is increased in metabolic dysfunction-associated steatotic liver disease and normalizes after bariatric surgery or GLP-1 therapy. iScience, 26(11), [108190]. https://doi.org/10.1016/j.isci.2023.108190

Vancouver

Kjeldsen SAS, Gluud LL, Werge MP, Pedersen JS, Bendtsen F, Alexiadou K et al. Neprilysin activity is increased in metabolic dysfunction-associated steatotic liver disease and normalizes after bariatric surgery or GLP-1 therapy. iScience. 2023;26(11). 108190. https://doi.org/10.1016/j.isci.2023.108190

Author

Kjeldsen, Sasha A.S. ; Gluud, Lise L. ; Werge, Mikkel P. ; Pedersen, Julie S. ; Bendtsen, Flemming ; Alexiadou, Kleopatra ; Tan, Tricia ; Torekov, Signe S. ; Iepsen, Eva W. ; Jensen, Nicole J. ; Richter, Michael M. ; Goetze, Jens P. ; Rungby, Jørgen ; Hartmann, Bolette ; Holst, Jens J. ; Holst, Birgitte ; Holt, Joachim ; Gustafsson, Finn ; Madsbad, Sten ; Svane, Maria S. ; Bojsen-Møller, Kirstine N. ; Wewer Albrechtsen, Nicolai J. / Neprilysin activity is increased in metabolic dysfunction-associated steatotic liver disease and normalizes after bariatric surgery or GLP-1 therapy. In: iScience. 2023 ; Vol. 26, No. 11.

Bibtex

@article{3b47daa1f0a04345b5803b94799a2840,
title = "Neprilysin activity is increased in metabolic dysfunction-associated steatotic liver disease and normalizes after bariatric surgery or GLP-1 therapy",
abstract = "Inhibitors of neprilysin improve glycemia in patients with heart failure and type 2 diabetes (T2D). The effect of weight loss by diet, surgery, or pharmacotherapy on neprilysin activity (NEPa) is unknown. We investigated circulating NEPa and neprilysin protein concentrations in obesity, T2D, metabolic dysfunction-associated steatotic liver disease (MASLD), and following bariatric surgery, or GLP-1-receptor-agonist therapy. NEPa, but not neprilysin protein, was enhanced in obesity, T2D, and MASLD. Notably, MASLD associated with NEPa independently of BMI and HbA1c. NEPa decreased after bariatric surgery with a concurrent increase in OGTT-stimulated GLP-1. Diet-induced weight loss did not affect NEPa, but individuals randomized to 52-week weight maintenance with liraglutide (1.2 mg/day) decreased NEPa, consistent with another study following 6-week liraglutide (3 mg/day). A 90-min GLP-1 infusion did not alter NEPa. Thus, MASLD may drive exaggerated NEPa, and lowered NEPa following bariatric surgery or liraglutide therapy may contribute to the reported improved cardiometabolic effects.",
keywords = "Diabetology, Health sciences, Obesity medicine",
author = "Kjeldsen, {Sasha A.S.} and Gluud, {Lise L.} and Werge, {Mikkel P.} and Pedersen, {Julie S.} and Flemming Bendtsen and Kleopatra Alexiadou and Tricia Tan and Torekov, {Signe S.} and Iepsen, {Eva W.} and Jensen, {Nicole J.} and Richter, {Michael M.} and Goetze, {Jens P.} and J{\o}rgen Rungby and Bolette Hartmann and Holst, {Jens J.} and Birgitte Holst and Joachim Holt and Finn Gustafsson and Sten Madsbad and Svane, {Maria S.} and Bojsen-M{\o}ller, {Kirstine N.} and {Wewer Albrechtsen}, {Nicolai J.}",
note = "Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
doi = "10.1016/j.isci.2023.108190",
language = "English",
volume = "26",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier",
number = "11",

}

RIS

TY - JOUR

T1 - Neprilysin activity is increased in metabolic dysfunction-associated steatotic liver disease and normalizes after bariatric surgery or GLP-1 therapy

AU - Kjeldsen, Sasha A.S.

AU - Gluud, Lise L.

AU - Werge, Mikkel P.

AU - Pedersen, Julie S.

AU - Bendtsen, Flemming

AU - Alexiadou, Kleopatra

AU - Tan, Tricia

AU - Torekov, Signe S.

AU - Iepsen, Eva W.

AU - Jensen, Nicole J.

AU - Richter, Michael M.

AU - Goetze, Jens P.

AU - Rungby, Jørgen

AU - Hartmann, Bolette

AU - Holst, Jens J.

AU - Holst, Birgitte

AU - Holt, Joachim

AU - Gustafsson, Finn

AU - Madsbad, Sten

AU - Svane, Maria S.

AU - Bojsen-Møller, Kirstine N.

AU - Wewer Albrechtsen, Nicolai J.

N1 - Publisher Copyright: © 2023 The Authors

PY - 2023

Y1 - 2023

N2 - Inhibitors of neprilysin improve glycemia in patients with heart failure and type 2 diabetes (T2D). The effect of weight loss by diet, surgery, or pharmacotherapy on neprilysin activity (NEPa) is unknown. We investigated circulating NEPa and neprilysin protein concentrations in obesity, T2D, metabolic dysfunction-associated steatotic liver disease (MASLD), and following bariatric surgery, or GLP-1-receptor-agonist therapy. NEPa, but not neprilysin protein, was enhanced in obesity, T2D, and MASLD. Notably, MASLD associated with NEPa independently of BMI and HbA1c. NEPa decreased after bariatric surgery with a concurrent increase in OGTT-stimulated GLP-1. Diet-induced weight loss did not affect NEPa, but individuals randomized to 52-week weight maintenance with liraglutide (1.2 mg/day) decreased NEPa, consistent with another study following 6-week liraglutide (3 mg/day). A 90-min GLP-1 infusion did not alter NEPa. Thus, MASLD may drive exaggerated NEPa, and lowered NEPa following bariatric surgery or liraglutide therapy may contribute to the reported improved cardiometabolic effects.

AB - Inhibitors of neprilysin improve glycemia in patients with heart failure and type 2 diabetes (T2D). The effect of weight loss by diet, surgery, or pharmacotherapy on neprilysin activity (NEPa) is unknown. We investigated circulating NEPa and neprilysin protein concentrations in obesity, T2D, metabolic dysfunction-associated steatotic liver disease (MASLD), and following bariatric surgery, or GLP-1-receptor-agonist therapy. NEPa, but not neprilysin protein, was enhanced in obesity, T2D, and MASLD. Notably, MASLD associated with NEPa independently of BMI and HbA1c. NEPa decreased after bariatric surgery with a concurrent increase in OGTT-stimulated GLP-1. Diet-induced weight loss did not affect NEPa, but individuals randomized to 52-week weight maintenance with liraglutide (1.2 mg/day) decreased NEPa, consistent with another study following 6-week liraglutide (3 mg/day). A 90-min GLP-1 infusion did not alter NEPa. Thus, MASLD may drive exaggerated NEPa, and lowered NEPa following bariatric surgery or liraglutide therapy may contribute to the reported improved cardiometabolic effects.

KW - Diabetology

KW - Health sciences

KW - Obesity medicine

UR - http://www.scopus.com/inward/record.url?scp=85175342309&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2023.108190

DO - 10.1016/j.isci.2023.108190

M3 - Journal article

C2 - 37953952

AN - SCOPUS:85175342309

VL - 26

JO - iScience

JF - iScience

SN - 2589-0042

IS - 11

M1 - 108190

ER -

ID: 372513597