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Haufe, S.* ; Kaminski, J.* ; Utz, W.* ; Haas, V.* ; Mähler, A.* ; Daniels, M.A.* ; Birkenfeld, A.L.* ; Lichtinghagen, R.* ; Luft, F.C.* ; Schulz-Menger, J.* ; Engeli, S.* ; Jordan, J.*

Differential response of the natriuretic peptide system to weight loss and exercise in overweight or obese patients.

J. Hypertens. 33, 1458-1464 (2015)

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OBJECTIVE: Relative atrial natriuretic peptide (ANP) deficiency has been implicated in the pathogenesis of obesity-associated cardiovascular and metabolic disease. We tested the hypothesis that more than 5% body weight reduction through 6 months hypocaloric dieting alters ANP release at rest and more so during exercise in overweight or obese patients. METHODS: Venous mid-regional pro-ANP concentration was assessed at rest and after incremental exhaustive exercise testing before and after weight reduction. We also measured natriuretic peptide receptor A and C mRNA expression in subcutaneous adipose tissue to gauge both ANP responsiveness and clearance mechanisms. RESULTS: The average weight reduction of 9.1 ± 3.8 kg was associated with reductions in visceral and subcutaneous abdominal fat mass, liver fat content, insulin resistance, and ambulatory blood pressure. However, mid-regional pro-ANP plasma concentrations were unchanged with weight loss (51 ± 24 vs. 53 ± 24 pmol/l). Exercise elicited similar acute mid-regional pro-ANP increases before and after weight loss. Adipose tissue natriuretic peptide receptor type A mRNA expression remained unchanged, whereas natriuretic peptide receptor type C mRNA decreased with weight loss. CONCLUSIONS: We conclude that physical exercise acutely increases ANP release in obese patients, whereas modest diet-induced weight loss primarily affects ANP clearance mechanisms. Interventions combining weight loss and regular physical exercise may be particularly efficacious in reversing obesity-associated relative natriuretic peptide deficiency.

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