Modulation of natriuretic peptide receptors in human adipose tissue: molecular mechanisms behind the “natriuretic handicap” in morbidly obese patients

Gentili, Alessandra; Frangione, Maria Rosaria; Albini, Elisa; Vacca, Carmine; Ricci, Maria Anastasia; Vuono, Stefano De; Boni, Marcello; Rondelli, Fabio; Rotelli, L; Lupattelli, Graziana; Orabona, Ciriana

doi:10.1016/j.trsl.2017.06.001

Cited by 31 publications

(26 citation statements)

References 24 publications

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“…Given that the ANP-dependent biological responses occur via its binding to NPRA, expressed in different type of immune cells [ 34 ], it has been reasonably suggested that, by autocrine/paracrine mechanisms [ 24 , 35 ], ANP exerts anti-inflammatory and immune-modulatory effects in the tissue microenvironment [ 20 ]. A similar biological effect based on similar molecular mechanisms, i.e., NF-κB and NALP3/ASC/Caspase-1 cascade inhibition, has been recently described for BNP [ 36 ], further supporting the anti-inflammatory role of this peptide [ 8 , 13 , 32 , 37 , 38 , 39 , 40 , 41 ]. As for direct effects on adaptive immunity, ANP/BNP reduce the number of CD4 + CD8 + lymphocytes while increasing the CD4 − CD8 − cells and stimulate the differentiation of naïve CD4 + cells toward the Th2 and/or Th17 phenotype [ 42 ].…”

Section: Natriuretic Peptides and The Immune Systemsupporting

confidence: 54%

Natriuretic Peptides: The Case of Prostate Cancer

et al. 2017

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Cardiac natriuretic peptides have long been known to act as main players in the homeostatic control of blood pressure, salt and water balance. However, in the last few decades, new properties have been ascribed to these hormones. A systematic review of English articles using MEDLINE Search terms included prostate cancer, inflammation, cardiac hormones, atrial natriuretic peptide, and brain natriuretic peptide. Most recent publications were selected. Natriuretic peptides are strongly connected to the immune system, whose two branches, innate and adaptive, are finely tuned and organized to kill invaders and repair injured tissues. These peptides control the immune response and act as anti-inflammatory and immune-modulatory agents. In addition, in cancers, natriuretic peptides have anti-proliferative effects by molecular mechanisms based on the inhibition/regulation of several pathways promoting cell proliferation and survival. Nowadays, it is accepted that chronic inflammation is a crucial player in prostate cancer development and progression. In this review, we summarize the current knowledge on the link between prostate cancer and inflammation and the potential use of natriuretic peptides as anti-inflammatory and anticancer agents.

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Section: Natriuretic Peptides and The Immune Systemsupporting

confidence: 54%

Natriuretic Peptides: The Case of Prostate Cancer

et al. 2017

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“…BNP and NT‐proBNP) secretion is either inhibited by factors released by adipose tissue or actively metabolized by clearance receptors (e.g. NPR‐C) in obese individuals . Van Kimmenade et al .…”

Section: Discussionmentioning

confidence: 99%

Sex‐specific associations of obesity and N‐terminal pro‐B‐type natriuretic peptide levels in the general population

Suthahar

Meijers

et al. 2018

European J of Heart Fail

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“…However, circulating BNP levels were lower under HFD as compared to ND, which is consistant with many published clinical and experimental studies showing that obese and type-2 diabetics display reduced circulating NP levels [ 5 ]. This has been linked to enhanced expression of the natriuretic peptide clearance receptor, NPR-C, in adipocytes [ 5 , 9 , 37 ]. Importantly, while these systemic effects of HFD (on blood pressure and BNP expression and circulation) were similar in control and β GC-A KO mice, islets freshly prepared from the later mice had markedly reduced cGMP contents, which is consistant with local ablation of the GC-A receptor.…”

Section: Discussionmentioning

confidence: 99%

“…However, endogenous NPs contribute to the control of glucose homeostasis under conditions of pathological diet-induced obesity by improving β-cell proliferation and function in early stages of enhanced insulin demand. Large prospective studies in nondiabetic individuals showed that low initial plasma levels of ANP or BNP predict development of future diabetes and glucose progression over time, suggesting a causal role of chronic NP deficiency in diabetes development [ 11 , 37 , 40 ]. Conversely, higher NT-proBNP is associated with decreased risk of incident diabetes even after adjustment for traditional risk factors [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

β Cell-specific deletion of guanylyl cyclase A, the receptor for atrial natriuretic peptide, accelerates obesity-induced glucose intolerance in mice

Tauscher

Nakagawa

Völker

et al. 2018

Cardiovasc Diabetol

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BackgroundThe cardiac hormones atrial (ANP) and B-type natriuretic peptides (BNP) moderate arterial blood pressure and improve energy metabolism as well as insulin sensitivity via their shared cGMP-producing guanylyl cyclase-A (GC-A) receptor. Obesity is associated with impaired NP/GC-A/cGMP signaling, which possibly contributes to the development of type 2 diabetes and its cardiometabolic complications. In vitro, synthetic ANP, via GC-A, stimulates glucose-dependent insulin release from cultured pancreatic islets and β-cell proliferation. However, the relevance for systemic glucose homeostasis in vivo is not known. To dissect whether the endogenous cardiac hormones modulate the secretory function and/or proliferation of β-cells under (patho)physiological conditions in vivo, here we generated a novel genetic mouse model with selective disruption of the GC-A receptor in β-cells.MethodsMice with a floxed GC-A gene were bred to Rip-CreTG mice, thereby deleting GC-A selectively in β-cells (β GC-A KO). Weight gain, glucose tolerance, insulin sensitivity, and glucose-stimulated insulin secretion were monitored in normal diet (ND)- and high-fat diet (HFD)-fed mice. β-cell size and number were measured by immunofluorescence-based islet morphometry.ResultsIn vitro, the insulinotropic and proliferative actions of ANP were abolished in islets isolated from β GC-A KO mice. Concordantly, in vivo, infusion of BNP mildly enhanced baseline plasma insulin levels and glucose-induced insulin secretion in control mice. This effect of exogenous BNP was abolished in β GC-A KO mice, corroborating the efficient inactivation of the GC-A receptor in β-cells. Despite this under physiological, ND conditions, fasted and fed insulin levels, glucose-induced insulin secretion, glucose tolerance and β-cell morphology were similar in β GC-A KO mice and control littermates. However, HFD-fed β GC-A KO animals had accelerated glucose intolerance and diminished adaptative β-cell proliferation.ConclusionsOur studies of β GC-A KO mice demonstrate that the cardiac hormones ANP and BNP do not modulate β-cell’s growth and secretory functions under physiological, normal dietary conditions. However, endogenous NP/GC-A signaling improves the initial adaptative response of β-cells to HFD-induced obesity. Impaired β-cell NP/GC-A signaling in obese individuals might contribute to the development of type 2 diabetes.

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Modulation of natriuretic peptide receptors in human adipose tissue: molecular mechanisms behind the “natriuretic handicap” in morbidly obese patients

Cited by 31 publications

References 24 publications

Natriuretic Peptides: The Case of Prostate Cancer

Natriuretic Peptides: The Case of Prostate Cancer

Sex‐specific associations of obesity and N‐terminal pro‐B‐type natriuretic peptide levels in the general population

β Cell-specific deletion of guanylyl cyclase A, the receptor for atrial natriuretic peptide, accelerates obesity-induced glucose intolerance in mice

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