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Low‐fat hypocaloric diet reduces neprilysin in overweight and obese human subjects

Henke, C. and Haufe, S. and Ziehl, D. and Bornstein, S.R. and Schulz‐Menger, J. and Heni, M. and Engeli, S. and Jordan, J. and Birkenfeld, A.L. (2021) Low‐fat hypocaloric diet reduces neprilysin in overweight and obese human subjects. ESC heart failure, 8 (2), pp. 938-942. Wiley. doi: 10.1002/ehf2.13220. ISSN 2055-5822.

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Official URL: http://dx.doi.org/10.1002/ehf2.13220


Aims Neprilysin (NEP), a zinc metallopeptidase, degrades a variety of bioactive peptides including natriuretic peptides terminating their biological action on arterial blood pressure and natriuresis. Pharmacological inhibition of NEP reduces mortality in patients with heart failure with reduced ejection fraction. Physiological interventions reducing NEP levels are unknown in humans. Because obesity leads to increased NEP levels and increases the risk for heart failure, we hypothesized that weight loss reduces NEP concentrations in plasma and tissue. Methods and results We randomized overweight to obese human subjects to a low‐fat or low‐carbohydrate hypocaloric 6 month weight loss intervention. Soluble NEP was determined in plasma, and NEP mRNA was analysed from subcutaneous adipose tissue before and after diet. Low‐fat diet‐induced weight loss reduced soluble NEP levels from 0.83 ± 0.18 to 0.72 ± 0.18 μg/L (P = 0.038), while subcutaneous adipose tissue NEP mRNA expression was reduced by both dietary interventions [21% (P = 0.0057) by low‐fat diet and 16% (P = 0.048) by low‐carbohydrate diet]. We also analysed the polymorphisms of the gene coding for NEP, rs9827586 and rs701109, known to be associated with plasma NEP levels. For both single‐nucleotide polymorphisms, minor allele carriers (A/A) had higher baseline plasma NEP levels (rs9827586: β = 0.53 ± 0.23, P < 0.0001; rs701109: β = 0.43 ± 0.22, P = 0.0016), and minor allele carriers of rs9827586 responded to weight loss with a larger NEP reduction (rs9827586: P = 0.0048). Conclusions Our study identifies weight loss via a hypocaloric low‐fat diet as the first physiological intervention in humans to reduce NEP in plasma and adipose tissue. Specific single‐nucleotide polymorphisms further contribute to the decrease. Our findings may help to explain the beneficial effect of weight loss on cardiac function in patients with heart failure.

Item URL in elib:https://elib.dlr.de/144547/
Document Type:Article
Title:Low‐fat hypocaloric diet reduces neprilysin in overweight and obese human subjects
AuthorsInstitution or Email of AuthorsAuthor's ORCID iDORCID Put Code
Henke, C.Dresden University School of Medicine, Technische Universität DresdenUNSPECIFIEDUNSPECIFIED
Haufe, S.Institute of Sports Medicine, Hannover Medical School, Hanover GermanyUNSPECIFIEDUNSPECIFIED
Ziehl, D.Section of Metabolic and Vascular Medicine, Medical Clinic III, University Hospital Carl Gustav Carus, TU Dresden, Dresden GermanyUNSPECIFIEDUNSPECIFIED
Bornstein, S.R.Section of Metabolic and Vascular Medicine, Medical Clinic III, Dresden University School of Medicine, Technische Universität Dresden, GermanyUNSPECIFIEDUNSPECIFIED
Schulz‐Menger, J.Experimental and Clinical Research Center (ECRC), a joint collaboration between Max Delbrück Center for Molecular Medicine and Charité—Universitätsmedizin Berlin, Berlin GermanyUNSPECIFIEDUNSPECIFIED
Heni, M.German Center for Diabetes Research (DZD e.V.), Neuherberg GermanyUNSPECIFIEDUNSPECIFIED
Engeli, S.Institute of Clinical Pharmacology, Hannover Medical School, Hannover, GermanyUNSPECIFIEDUNSPECIFIED
Jordan, J.UNSPECIFIEDhttps://orcid.org/0000-0003-4518-0706UNSPECIFIED
Birkenfeld, A.L.University Hospital Carl-Gustav Carus, Dresden, GermanyUNSPECIFIEDUNSPECIFIED
Date:27 February 2021
Journal or Publication Title:ESC heart failure
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In ISI Web of Science:Yes
Page Range:pp. 938-942
Keywords:Neprilysin; Hypocaloric low‐fat diet; Natriuretic peptides; Heart failure
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Research under Space Conditions
DLR - Research theme (Project):R - CardioBrain
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine
Institute of Aerospace Medicine > Leitungsbereich ME
Deposited By: Schrage, Larissa
Deposited On:21 Oct 2021 11:11
Last Modified:22 Oct 2021 11:25

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