Increasing energy expenditure via brown adipose tissue (BAT) thermogenesis is a possible therapeutic strategy to treat obesity and its associated co-morbidities. The thiazolidinedione class of anti-hyperglycemic drugs increase BAT differentiation in pre-clinical experimental models and therefore potentially increase BAT thermogenic capacity. Thus, the aim of the study was to determine if pioglitazone treatment for 4 weeks increases BAT activity in response to acute cold exposure in humans. In a double-blinded, placebo-controlled, parallel design trial, 14 lean (BMI <25 kg/m2), un-medicated male participants who exercise <2 hours per week and were free of overt cardiovascular and metabolic disease were randomised to receive placebo (lactose) or pioglitazone (45mg/day) for 28 days. After unblinding in September 2016, this presentation will report the primary outcome measure of the change in BAT activity in response to acute cold exposure, assessed before and after the interventions by measuring glucose uptake with 18F-fluorodeoxyglucose Positron Emission Tomography-Computerised Tomography (PET-CT). BAT activity will be measured in regions of supraclavicular adipose tissue with radiodensity corresponding to BAT and reported as maximum and mean standardised glucose uptake value (SUVmax and SUVmean). Energy expenditure, cardiovascular responses (blood pressure and heart rate), core temperature, blood glucose, plasma non-esterified fatty acids and plasma noradrenaline will also be reported basally and in response to acute cold exposure along with body composition before and after the intervention. Outcomes from the study will expand our understanding of human BAT physiology and inform the development of therapeutic approaches that target energy expenditure via BAT.