Objective: Atrial natriuretic peptide (ANP) regulates arterial blood pressure. In addition, ANP has recently been shown to promote human adipose tissue lipolysis through cGMP-mediated hormone-sensitive lipase activation. We hypothesized that ANP increases postprandial free fatty acid (FFA) availability and energy expenditure while decreasing arterial blood pressure.

Research design and methods: We infused human ANP (25 ng . kg(-1) . min(-1)) in 12 men (age 32 +/- 0.8 years, BMI 23.3 +/- 0.4 kg/m(2)) before, during, and 2 h after ingestion of a standardized high-fat test meal in a randomized, double-blind, cross-over fashion. Cardiovascular changes were monitored by continuous electrocardiogram and beat-by-beat blood pressure recordings. Metabolism was monitored through venous blood sampling, intramuscular and subcutaneous abdominal adipose tissue microdialysis, and indirect calorimetry.

Results: ANP infusion decreased mean arterial blood pressure by 4 mmHg during the postprandial phase (P < 0.01 vs. placebo). At the same time, ANP induced lipolysis systemically (P < 0.05 vs. placebo) and locally in subcutaneous abdominal adipose tissue (P < 0.0001 vs. placebo), leading to a 50% increase in venous glycerol (P < 0.01) and FFA (P < 0.05) concentrations compared with placebo. The increase in FFA availability with ANP was paralleled by a 15% increase in lipid oxidation rates (P < 0.05 vs. placebo), driving a substantial increase in postprandial energy expenditure (P < 0.05 vs. placebo).

Conclusions: Our data identify the ANP system as a novel pathway regulating postprandial lipid oxidation, energy expenditure, and concomitantly arterial blood pressure. The findings could have therapeutic implications.