Diabetologie und Stoffwechsel 2016; 11 - LB8
DOI: 10.1055/s-0036-1584102

A novel heart-adipose tissue axis: Atrial natriuretic peptide and leptin interactions in man

J Jordan 1, P Fischer-Posovszky 2, J Reinke 3, M Daniels 3, M Wabitsch 2, S Engeli 1, AL Birkenfeld 3, 4, 5
  • 1Medizinische Hochschule Hannover, Institut für Klinische Pharmakologie, Hannover, Germany
  • 2Ulm University Medical Center, Department of Pediatrics and Adolescent Medicine, Ulm, Germany
  • 3Technische Universität Dresden, Metabolisch Vaskuläre Medizin, Dresden, Germany
  • 4GWT-TUD GmbH, Kompetenz Zentrum für Metabolisch Vaskuläre Medizin, Dresden, Germany
  • 5Kings College London, London, United Kingdom

Increased levels of leptin are common features of obesity and type 2 diabetes, reflecting leptin resistance. Reduced circulating natriuretic peptide (NP) concentrations are independently associated with type 2 diabetes and obesity, while increased natriuretic peptide levels appear to be protective. Observational studies suggest that high NP levels are associated with reduced leptin concentrations. Whether or not this is a causal relationship is unknown.

We tested the hypothesis that atrial natriuretic peptide (ANP) acutely decreases leptin levels in 12 healthy men. We infused ANP intravenously over 135 minutes while collecting venous blood and adipose tissue microdialysates at baseline and at the end of ANP-infusion. Blood samples were also obtained identically without ANP infusion in 7 age and BMI matched men. Moreover, ANP effects on leptin secretion were tested in human SGBS adipocytes in vitro.

With infusion, ANP concentrations increased 10 fold. Systemic and adipose tissue glycerol concentrations increased 70% and 80%, respectively (P < 0.01). ANP infusion decreased systemic leptin levels from 3.6 ± 1 ng/ml to 3.3 ± 1 ng/ml (P = 0.01, 12% decrease). Leptin levels did not change in the control group (P < 0.05 vs. infusion). ANP markedly reduced leptin release in human SGBS adipocytes, without changes in mRNA expression.

Our data show that the cardiac hormone ANP acutely decrease systemic leptin concentrations in healthy subjects. Our in vitro data suggest that the effect is mediated via inhibition of leptin release. Our study has implications for the physiological regulation of leptin in conditions with altered NP availability, such as type 2 diabetes and obesity.