PLoS One. 2013 Aug 29;8(8):e72959.

Impact of obesity on the expression profile of natriuretic peptide system in a rat experimental model.

Cabiati M, Raucci S, Liistro T, Belcastro E, Prescimone T, Caselli C, Matteucci M, Iozzo P, Mattii L, Giannessi D, Del Ry S.

Laboratory of Cardiovascular Biochemistry,  CNR Institute of Clinical Physiology, Pisa, Italy.

 

Abstract

Natriuretic peptides (NPs) play an important role in obesity and aim of this study was to evaluate, in cardiac tissue of obese Zucker rats (O, n = 29) their transcriptomic profile compared to controls (CO, n = 24) by Real-Time PCR study; CNP protein expression was evaluated by immunostaining and immunometric tests. Myocardial histology was performed, confirming no alteration of organ structure. While ANP and BNP are cardiac peptides, CNP is mainly an endothelial hormone; thus its expression, as well as that of NPR-B and NPR-C, was also evaluated in kidney and lung of an animal subgroup (n = 20). In heart, lower BNP mRNA levels in O vs CO (p = 0.02) as well as ANP and CNP (p = ns), were detected. NPR-B/NPR-A mRNA was similar in O and CO, while NPR-C was numerically lower (p = ns) in O than in CO. In kidney, CNP/NPR-B/NPR-C mRNA was similar in O and CO, while in lung CNP/NPR-C expression decreased and NPR-B increased (p = ns) in O vs CO. Subdividing into fasting and hyperglycemic rats, the pattern of mRNA expression for each gene analyzed remained unchanged. The trend observed in heart, kidney and lung for CNP protein concentrations and immunohistochemistry reflected the mRNA expression. TNF-α and IL-6 mRNA were measured in each tissue and no significant genotype effect was detected in any tissue. The main NP variations were observed at the cardiac level, suggesting a reduced release by cardiac cells. The understanding of mechanisms involved in the modulation of the NP system in obesity could be a useful starting point for future clinical study devoted to identifying new obesity treatment strategies.

PMID: 24009719

 

Supplement:

It was recently shown that natriuretic peptides play a central role in the regulation of body weight and energy metabolism (1) (Fig. 1) and it was demonstrated that ANP and BNP are significantly lower in over­weight adult obese patients than in lean patients, probably contributing to both the genesis of insulin resistance and to the pathophysiology of hypertension. Fig 1Most obese adults were obese as adolescents and most adolescents were overweight and/or obese as children. In fact, the origins of obesity are being traced to early childhood development. Childhood obesity is a worldwide health problem and its prevalence is increasing steadily and dramatically all over the world ( Fig 2).

Fig 2

Obese subjects have a much greater likelihood than normal-weight children of acquiring dyslipidemia, elevated blood pressure and impaired glucose metabolism, which significantly increase their risk of cardiovascular and metabolic diseases. Childhood obesity is also a major risk factor for the early onset of endothelial dysfunction and atherosclerosis. In our laboratory, we focused our efforts on the study of the natriuretic peptides in obese children (2); we observed that overweight and obese children have significantly lower CNP plasma levels compared with lean subjects (Fig 3a).  BNP plasma levels measured in the same subjects also resulted lower (Fig.3b), confirming reports from previous investigators in obese adults and suggesting a defective natriuretic peptide system in these patients.

fig3Given the involvement of natriuretic peptides in obesity it becomes extremely important to have age-specific reference intervals for this peptide also for pediatric subjects.

Recently, in our laboratory, a rapid and easy procedure for the preparation of total cellular RNA from a minimal amount of human whole blood was developed allowing the simultaneous transcriptomic evaluation of several genes (3,4,5,6).

In the evaluation of new biomarkers following the molecular medicine approach, expression, production, release and function can provide further relevant information allowing a more complete interpretation. Actually in our laboratory new experiments  are carried out in obese adolescents to evaluate the transcriptomic profiling of natriuretic peptides as also as of new cardiovascular biomarkers.

fig 4

The availability of drugs promoting the actions of natriuretic peptides or other biomarkers may theoretically be an attractive therapeutic option to prevent cardiovascular disease.

 

References:

  1. Moro C, Smith SR. Natriuretic peptides: new players in energy homeostasis. Diabetes 2009; 58: 2726-2728.
  2. Del Ry S, Cabiati M, Bianchi V, Storti S, Caselli C, Prescimone T, Clerico A, Saggese G, Giannessi D, Federico G. C-type natriuretic peptide plasma levels are reduced in obese adolescents. Peptides. 2013;50:50-4.
  3. Sabatino L, Cabiati M, Caselli C, Del Ry S. Adenosine receptor expression and gene reference evaluation in human leukocytes. Clin Lab. 2013;59(5-6):571-7.
  4. Cabiati M, Sabatino L, Caruso R, Caselli C, Prescimone T, Giannessi D, Del Ry S. Gene expression of C-type natriuretic peptide and of its specific receptor NPR-B in human leukocytes of healthy and heart failure subjects. Peptides. 2012 ;37(2):240-6.
  5. Cabiati M, Sabatino L, Caruso R, Verde A, Caselli C, Prescimone T, Giannessi D, Del Ry S. C-type natriuretic peptide transcriptomic profiling increases in human leukocytes of patients with chronic heart failure as a function of clinical severity. Peptides. 2013 Sep;47:110-4.
  6. Cabiati M, Caruso R, Verde A, Sabatino L, Morales MA, Del Ry S. Transcriptomic profiling of the four adenosine receptors in human leukocytes of heart failure patients. Biomed Res Int. 2013;2013:569438.

 

Acknowledgements:  This study was conducted within the context of the project entitled “Early diagnosis of organ metabolic and inflammatory damage related with cancer and cardio-metabolic risk in childhood obesity. Validation of panel-oriented biomarkers in obese animals and implementation in children and adolescents” (Unique Project Code B55E09000560002), supported by the Regione Toscana (Tuscany Region) under the Research Call “Innovation in Medicine 2009”.

 

Contact:
Dr. Silvia Del Ry, ScD

CNR Institute of Clinical Physiology

Via Giuseppe Moruzzi 1, 56124 Pisa – Italy

Tel: +39 050 3152793 – Fax +39 050 3152166

e-mail: delry@ifc.cnr.it

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