Norepinephrine transporter function and autonomic control of metabolism

Area of Science:

• Pharmacology
• Metabolic Science
• Adipose Tissue Biology

Background:

• Norepinephrine transporter (NET) function is influenced by genetics and drugs, but its metabolic effects are unclear.
• Understanding NET inhibition's metabolic consequences is crucial for pharmacology and metabolic research.

Purpose of the Study:

• To investigate the metabolic effects of acute NET inhibition using a selective NET inhibitor, reboxetine.
• To determine how NET inhibition impacts energy expenditure, substrate oxidation, and adipose tissue metabolism.

Main Methods:

• A randomized, double-blind, cross-over trial involving 15 healthy subjects treated with reboxetine or placebo.
• Indirect calorimetry assessed energy expenditure and substrate oxidation during isoproterenol infusion.
• Adipose tissue metabolism was analyzed via microdialysis during isoproterenol perfusion.

Main Results:

• NET inhibition did not alter resting energy expenditure or substrate oxidation.
• During isoproterenol stimulation, carbohydrate oxidation was higher with reboxetine.
• Reboxetine increased adipose tissue blood flow, glucose uptake, metabolism, and lipid mobilization, but decreased overall lipid oxidation.

Conclusions:

• Acute NET inhibition enhances adipose tissue glucose metabolism and lipid mobilization.
• NET inhibition sensitizes adipose tissue to beta-adrenergic stimulation, impacting substrate utilization.
• The observed effects are independent of systemic or local norepinephrine level changes.