Lipolytic effects of B-type natriuretic peptide 1-32 in adipose tissue of heart failure patients compared with healthy controls

Objectives: Our goal was to examine the role of B-type natriuretic peptide (BNP) in lipolysis regulation in heart failure (HF) patients.

Background: Enhanced adipose tissue lipolysis can contribute to myocardial lipid overload, insulin resistance, and cachexia in advanced HF. Natriuretic peptides were recently recognized to stimulate lipolysis in healthy subjects.

Methods: Ten nondiabetic HF patients (New York Heart Association functional class III, 50% nonischemic etiology) and 13 healthy subjects (control subjects) of similar age, sex, and body composition underwent a microdialysis study of subcutaneous abdominal adipose tissue. Four microdialysis probes were simultaneously perfused with 0.1 μM BNP(1-32,) 10 μM BNP(1-32), 10 μM norepinephrine (NE) or Ringer's solution. Outgoing dialysate glycerol concentration (DGC) was measured as an index of lipolysis.

Results: Spontaneous lipolysis was higher in HF patients compared with control subjects (DGC: 189 ± 37 μmol/l vs. 152 ± 35 μmol/l, p < 0.01). Response to NE was similar (p = 0.35) in HF patients and control subjects (DGC increase of 1.7 ± 0.2-fold vs. 1.7 ± 0.4-fold). BNP(1-32) 10 μM markedly increased lipolysis in both HF patients and control subjects (DGC increase of 2.8 ± 0.5-fold vs. 3.2 ± 0.3-fold), whereas the response to 0.1 μM BNP(1-32) was more pronounced in HF patients (p = 0.02). In HF patients, spontaneous lipolysis positively correlated with insulin resistance and the response to BNP(1-32) negatively correlated with adiposity.

Conclusions: BNP(1-32) exerts strong lipolytic effects in humans. Despite marked elevation of plasma immunoreactive BNP, the responsiveness of adipose tissue to BNP(1-32) is not attenuated in HF, possibly reflecting a deficiency of endogenous bioactive BNP. Lipolytic effects of BNP can contribute to excessive fatty acid mobilization in advanced HF.