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

Abstract

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.

2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension

“…In the TONE trial, moderate weight loss decreased the need for antihypertensive therapy by approximately 30% in older hypertensive patients on a single antihypertensive drug [1469]. The BP-lowering effects of weight reduction achieved by dietary approaches are also supported by meta-analyses [1470], and evidence is available that loss of body weight reduces sympathetic activity [367], while reversing abnormalities in natriuretic peptide regulation [1471,1472]. Thus, lifestyle interventions aimed at reducing body weight are recommended in patients with obesity and hypertension through low caloric diets and increased physical activity.…”

Geographic variation in dementia-related adverse events associated with sacubitril/valsartan: Analysis of the FDA Adverse Event Reporting System

“…5 In the case of rs701109, patients with the alternative allele had signi cantly higher neprilysin protein levels, which might result in the promotion of amyloid-β degradation. 10,17 There are other factors that may have impacted our ndings of continental differences in dementiarelated AEs. Epidemiologic research on dementia and Alzheimer's disease suggests that the prevalence is higher in North America than in Asia, Africa, and Latin America.…”

Adipolin, Chemerin, Neprilysin and Metabolic Disorders Associated with Obesity

“…In contrast, Henke et al investigated how blood neprilysin concentrations were affected by a six-month weight-reduction diet leading to weight loss. The researchers showed a significant decrease in blood levels of this adipokine due to the dietary intervention in the low-fat diet group, which they did not find with the low-carbohydrate diet, despite comparable weight loss in both groups [27]. On this basis, it can be suggested that neprilysin concentrations depend more on the diet (which can lead to weight gain or loss) than on the subjects' weight.…”