1. Neprilysin activity is increased in metabolic dysfunction-associated steatotic liver disease and normalizes after bariatric surgery or GLP-1 therapy.
- Author
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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, and Wewer Albrechtsen NJ
- 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., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)
- Published
- 2023
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