Metabolic Effects of Natriuretic Peptide Hormones
Condition: Obesity; Cardiovascular Physiological Phenomena; Metabolism
MeSH terms: Obesity
Intervention: recombinant human BNP(1-32); placebo (control, normal saline)
Intervention description: Subjects will receive an IV infusion of recombinant human BNP(1-32) for 240 minutes at a rate of 10 ng/kg/minute for 240 minutes, preceded by an IV bolus of 100 ng/kg.; Subjects will receive an IV infusion of placebo (normal saline) at a rate of 10 ng/kg/minute for 240 minutes, preceded by an IV bolus of 100 ng/kg.
Intervention MeSH terms: Natriuretic Peptide, Brain
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: In this cross-over study, each subject will receive BNP infusion at one visit and placebo (control) at the other visit, in random order. The sequence of the treatments will be randomized. There will be a washout period (at least 14 days) between visits.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking description: The participant and study investigators will be blinded as to which infusion the participant is receiving at which visit. Also, the individuals analyzing the energy expenditure and fat gene expression will be blinded.
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: obesity; Cardiovascular Physiological Phenomena; metabolism; Energy Metabolism

Summary:

      Accumulating evidence suggests that the natriuretic peptide (NP) hormonal system has
      important effects on metabolism. However, more information is needed to better understand the
      effects of NPs on metabolism in humans. Therefore, the investigators propose a study to
      determine the effects of b-type natriuretic peptide (BNP) on energy and fat metabolism in
      humans. The investigators' primary hypothesis is that the administration of BNP will increase
      energy expenditure in humans. The investigators' secondary hypothesis is that BNP
      administration will promote changes in gene expression in fat tissue suggestive of fat
      "beiging" in humans. Interventions that safely increase energy expenditure and promote fat
      "beiging" represent potential strategies for treating metabolic dysfunction due to obesity.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women ages 18-40 years

          -  Body Mass Index (BMI): 18.5 BMI<25 kg/m2 (lean) or BMI > or = 30 kg/m2 (obese)

        Exclusion Criteria:

          -  Significant cardiovascular disease (including heart failure and atrial fibrillation)

          -  Significant pulmonary, liver, or renal disease

          -  Diabetes Mellitus

          -  Significant Hypertension

          -  Hypotension

          -  Thyroid dysfunction

          -  Active malignancy

          -  Current or recent use of glucocorticoids

          -  Current use of antihypertensive medications, including diuretics

          -  Current use of medications affecting glucose metabolism, including metformin

          -  Current use of amphetamines or other medications known to affect energy homeostasis

          -  Currently pregnant or breastfeeding, or unwilling to avoid becoming pregnant or
             breastfeeding during study duration

          -  Significant claustrophobia that would prevent the use of the metabolic cart as part of
             the study protocol

          -  Currently abnormal serum or plasma sodium or potassium level

          -  Known hypersensitivity to recombinant human b-type natriuretic peptide, BNP(1-32)
             (nesiritide), or phenylephrine

          -  Hemoglobin A1c (HbA1c) >= 6.5%

          -  Liver Function Tests (LFTs) elevated >2x upper limit of normal

          -  Estimated Glomerular Filtration Rate (eGFR) <60 ml/min

          -  Currently abnormal thyroid stimulating hormone (TSH)