Treatment with brain natriuretic peptide prevents the development of cardiac dysfunction in obese diabetic db/db mice

Plante, Eric; Ménaouar, Ahmed; Danalache, Bogdan; Broderick, Tom L.; Jankowski, Marek; Gutkowska, Jolanta

doi:10.1007/s00125-014-3201-4

Cited by 69 publications

(62 citation statements)

References 36 publications

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“…In keeping with this hypothesis, cardiac mRNA expression of both ANP and BNP is reduced in obese Zucker fatty rats and db/db mice (50,55). Data in humans are limited; however, a study in subjects who underwent cardiac catheterization has shown that cardiac BNP release is inversely and independently related to BMI (56).…”

Section: Nps and Obesity Diabetes And Diabetes Complications Obesitymentioning

confidence: 65%

“…Indeed, in obese and insulin-resistant subjects, reduced ANP and BNP levels and upregulation of the clearance NPR-C in the adipose tissue may hamper the ability of the local NP system to enhance lipolysis and energy expenditure (5). In keeping with this hypothesis, targeted deletion of the NPR-C gene in rodents results in a lean phenotype, transgenic BNP mice fed with a high-fat diet are protected from obesity and insulin resistance, and chronic BNP infusion improves the metabolic profile of db/db mice, including a reduction in fat content (32,40,50).…”

Section: Nps and Obesity Diabetes And Diabetes Complications Obesitymentioning

confidence: 74%

“…This suggests that HF, particularly in diabetes, affects either the expression and activity of proBNP cleaving enzymes or proBNP glycosylation, a modification that changes proBNP susceptibility to cleavage by furin, particularly when it occurs at Thr71 (25). On the other hand, studies in db/db mice suggest that both enhanced BNP3-32 formation and resistance to mechanisms of proBNP clearance from the circulation also may contribute to increase circulating BNP immunoreactivity in diabetes (50).…”

Section: Diabetes Complicationsmentioning

confidence: 97%

“…These physiological studies do not, however, address the far more relevant issue of the long-term effects of chronic NP treatment on glucose metabolism. This has not yet been investigated in humans; however, a recent study in db/db mice has shown that chronic BNP infusion induces a significant reduction in blood glucose levels (50).…”

Section: Biological Actions Of Nps and Metabolismmentioning

confidence: 99%

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Natriuretic Peptides, Heart, and Adipose Tissue: New Findings and Future Developments for Diabetes Research

2014

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Natriuretic peptides (NPs) play a key role in cardiovascular homeostasis, counteracting the deleterious effects of volume and pressure overload and activating antibrotic and antihypertrophic pathways in the heart. N-terminal B-type NP (NT-proBNP) also is a promising biomarker of global cardiovascular risk in the general population, and there is increasing interest on its potential use in diabetic patients for screening of silent cardiovascular abnormalities, cardiovascular risk stratification, and guided intervention. Recently, both atrial NP (ANP) and B-type NP (BNP) have emerged as key mediators in the control of metabolic processes including the heart in the network of organs that regulate energy usage and metabolism. Epidemiological studies have shown that ANP and BNP are reduced in people with obesity, insulin resistance, and diabetes, and this deficiency may contribute to enhance their global cardiovascular risk. Moreover, ANP and BNP have receptors in the adipose tissue, enhance lipolysis and energy expenditure, and modulate adipokine release and food intake. Therefore, low ANP and BNP levels may be not only a consequence but also a cause of obesity, and recent prospective studies have shown that low levels of NT-proBNP and midregional proANP (MR-proANP) are a strong predictor of type 2 diabetes onset. Whether ANP and BNP supplementation may result in either cardiovascular or metabolic benefits in humans remains, however, to be established.Natriuretic peptides (NPs) have gained great interest as indicators of the state of cardiovascular health across the spectrum of cardiovascular diseases (CVD) in diabetic subjects (1-4). Recently, NPs also have emerged as key mediators in the control of metabolic processes (5) and have been implicated in the development of diabetes (6,7), shifting current paradigms and opening novel avenues in diabetes research. This review will summarize new findings in the field and discuss their potential clinical relevance. NPS AND THEIR RECEPTORSNPs are a family of genetically distinct and structurally related peptides, including atrial NP (ANP), B-type NP (BNP), and C-type NP (CNP). They share a similar structural conformation, characterized by a peptide ring with a cysteine bridge, which is well preserved throughout evolution, being the portion of the chain that binds to the receptor. ANP and BNP are predominantly secreted by cardiomyocytes, whereas CNP is mainly produced by the central nervous system, the endothelium, the bone, and the reproductive system (8-11).

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Section: Nps and Obesity Diabetes And Diabetes Complications Obesitymentioning

confidence: 65%

Section: Nps and Obesity Diabetes And Diabetes Complications Obesitymentioning

confidence: 74%

Section: Diabetes Complicationsmentioning

confidence: 97%

Section: Biological Actions Of Nps and Metabolismmentioning

confidence: 99%

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Natriuretic Peptides, Heart, and Adipose Tissue: New Findings and Future Developments for Diabetes Research

2014

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“…This was associated with increased muscle mitochondrial biogenesis and fat oxidation through upregulation of PPAR‐γ coactivator PGC‐1α and PPAR‐δ. Furthermore, chronic BNP treatment at low dose reduced plasma glucose levels, improved metabolic profile, and prevented development of myocardial dysfunction in obese diabetic mice 100. When BNP levels were determined from HF patients, obese patients indeed had reduced BNP plasma levels, although no difference in severity of HF or proinflammatory cytokine levels were detected 101…”

Section: Natriuretic Peptides In the Regulation Of Energy Metabolismmentioning

confidence: 98%

Natriuretic Peptides in the Regulation of Cardiovascular Physiology and Metabolic Events

Kerkelä

Ulvila

Magga

2015

JAHA

126

108

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Six‐year changes in N‐terminal pro‐brain natriuretic peptide and changes in weight and risk of obesity

Silva

Lazo

Tang

et al. 2021

Obesity

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ObjectiveThe aim of this study was to study the prospective association between N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and changes in weight and obesity risk in a community‐based population.MethodsData from 9,681 participants from the Atherosclerosis Risk in Communities Study were analyzed at two time points 6 years apart. Among people without obesity at baseline, multivariable logistic regression models were used to examine the association between baseline levels of NT‐proBNP and incident obesity. A multivariable linear regression model was used to examine the association between changes in NT‐proBNP (visit 2 serum and visit 4 plasma samples) and changes in weight.ResultsThe prevalence of obesity increased from 28% to 35% in the 6‐year follow‐up period. Compared with individuals in the highest NT‐proBNP quartile, those in the lowest were more likely to have obesity at baseline (odds ratio 1.25; 95% CI: 1.08‐1.45) and, among people who did not have obesity at baseline, were more likely to develop obesity at follow‐up (odds ratio 1.35; 95% CI: 1.07‐1.69). Changes in NT‐proBNP were inversely associated with weight change.ConclusionsIn this prospective study, lower levels of NT‐proBNP were associated with higher risk of obesity, and changes in NT‐proBNP were inversely associated with changes in weight. This suggests that natriuretic peptides or their pathways may be potential targets in the treatment of obesity.

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Treatment with brain natriuretic peptide prevents the development of cardiac dysfunction in obese diabetic db/db mice

Abstract: Our results indicate that chronic BNP treatment at low dose improves the metabolic profile and prevents the development of myocardial dysfunction in db/db mice.

Cited by 69 publications

References 36 publications

Natriuretic Peptides, Heart, and Adipose Tissue: New Findings and Future Developments for Diabetes Research

Natriuretic Peptides, Heart, and Adipose Tissue: New Findings and Future Developments for Diabetes Research

Natriuretic Peptides in the Regulation of Cardiovascular Physiology and Metabolic Events

Six‐year changes in N‐terminal pro‐brain natriuretic peptide and changes in weight and risk of obesity

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