Activation of Brown Adipose Tissue Thermogenesis in Humans Using Formoterol Fumarate (GB10)
Status:
Recruiting
Trial end date:
2024-09-01
Target enrollment:
Participant gender:
Summary
One emerging, highly modifiable homeostatic mechanism for energy expenditure in humans is
brown adipose tissue (BAT) thermogenesis. BAT is currently considered a prime target for the
treatment of obesity and Type 2 diabetes (T2D).
Using acetate and fluorodeoxyglucose (FDG) positron emission tomography (PET) , It has been
demonstrated that BAT thermogenesis is inducible by chronic cold exposure.
BAT activation through cold exposure is associated with improved glucose homeostasis and
insulin sensitivity.
A pharmaceutical approach, which seemed to be very promising to stimulate the activation of
BAT, was the use of a selective beta 3-adrenergic receptor agonist, mirabegron. Nevertheless,
in a later study, It has been demonstrated that human BAT thermogenesis is under the control
of beta-2, not beta-3, adrenergic receptor. The most selective beta-2 adrenergic receptor
agonist approved for clinical use in Canada is formoterol fumarate, given in inhalation for
the treatment of asthma (Oxeze®).
In summary, BAT contributes to cold-induced thermogenesis and is recruited by chronic cold
exposure as well as by a growing number of food supplements and drugs. Intracellular
triglyceride (TG) is the primary source of fuel for BAT thermogenesis under normal
physiological conditions, as blocking intracellular TG lipolysis using nicotinic acid
abolishes BAT thermogenesis. Beta-2 adrenergic stimulation is the pharmacological target to
activate BAT thermogenesis in humans and may also lead to white adipose tissue lipolysis.
Using a highly-selective beta-2 receptor agonist with and without administration of nicotinic
acid would thus give the opportunity to quantify more precisely energy expenditure accounted
by BAT thermogenesis and white adipose tissue metabolism in humans.