The Effect of Brown Adipose Tissue Activation on Insulin Sensitivity in Humans

Recent findings document the presence of active brown adipose tissue (BAT) in humans. Cold
exposure via adrenergic stimulation activates BAT, which combusts significant amounts of
blood glucose and free fatty acid (FFA) to produce heat. Animal studies suggest that BAT
activation improves insulin sensitivity. However, the effect of cold-induced BAT activation
on insulin sensitivity and glucose kinetics in humans remains unknown. The investigators'
central hypothesis is that cold-induced BAT activation increases whole body insulin
sensitivity in humans via augmented plasma glucose and FFA clearance. The specific aims of
this study are to define the effects of prolonged (8h) cold exposure BAT activation on:
insulin sensitivity (Aim 1); lipolysis and plasma glucose and FFA kinetics (Aim 2); on
thermoregulation (Aim 3). Moreover, the investigators plan to investigate for alternative
ways, which can activate BAT including cold water ingestion, a single meal ingestion, and a
single bout of moderate intensity exercise (Aim 4). For the cold exposure study, subjects
will complete 3 trials: a) 8hrs of cold exposure at their individually determined shivering
threshold; b) 8hrs of cold exposure at their individually determined shivering threshold plus
propranolol; c) 8hrs in thermoneutral conditions (26 - 28°C). For the rest of the arms of
subjects will complete two trials: cold or tepid water ingestion, a single meal ingestion or
no food ingestion, and a single bout of moderate intensity exercise or no exercise.To study
the above aims, the investigators will use positron emission tomography - computed
tomography, hyperinsulinemic euglycemic clamp, infusion of stable isotopes, and tissue
biopsies. The findings will illuminate the role of BAT on plasma substrate regulation and
insulin sensitivity and may aid in the development of lifestyle recommendations and
pharmacotherapy for the prevention and treatment of diabetes and insulin resistance.