Context: Atrial natriuretic peptide (ANP) in pharmacological concentrations stimulates lipid mobilization in humans.

Objective: The objective was to determine the hemodynamic and metabolic response to physiologically relevant ANP concentrations.

Design: The design was a human physiological study, conducted in 2004.

Setting: The study was conducted at an academic research institute.

Participants: Fourteen healthy normal-weight men (30 ± 1.2 yr) participated in the study.

Intervention: Intravenous infusion of human ANP (h-ANP) was administered at rates of 6.25, 12.5, and 25 ng/kg·min.

Main Outcome Measures: We studied local changes in blood flow and glucose and lipid metabolism of abdominal sc adipose tissue and femoral skeletal muscle by microdialysis. Overall changes in energy expenditure and substrate oxidation rates were monitored by indirect calorimetry.

Results: The increase in serum nonesterified fatty acids and glycerol concentrations were correlated with ANP plasma concentrations (r² = 0.86 and r² = 0.76, respectively). In adipose tissue, glycerol increased from 53 ± 6 μmol/liter to 87±13 μmol/liter (P < 0.001). In femoral skeletal muscle, glycerol concentrations did not change, whereas lactate-to-pyruvate ratio decreased from 91 ± 23 to 32 ± 4 (P < 0.001). Indirect calorimetry indicated an increase in lipid oxidation (P < 0.05) concomitantly with a decrease in carbohydrate oxidation (P < 0.01), without changes in overall energy expenditure.

Conclusions: ANP briskly stimulates lipid mobilization and oxidation at plasma concentrations that are encountered in conditions such as heart failure. Natriuretic-peptide induced lipid mobilization might contribute to cardiac cachexia. Drugs that interfere with the natriuretic peptide system should be evaluated for potential metabolic side effects.