Current estimates indicate that 8% of adults are diabetic world-wide, a large proportion of which live in the developing world. Existing therapies are unable to provide durable and robust change in metabolic status, thus there remains an imperative to identify novel therapeutic agents able to effect meaningful metabolic change in this patient population. Antibody-mediated targeting of fibroblast growth factor receptor 1 (FGFR1) has been shown to ameliorate hyperglycaemia and protect from diet and genetically induced obesity in rodents. Specifically, we have previously reported that administration of a monoclonal antibody (IMC-H7) which selectively targets the FGFR1c isoform, acts centrally to lower caloric intake and ultimately reduce body weight in an natural animal model of obesity, the Siberian hamster. However, it is currently unknown which tissue(s) contribute to these effects following administration of these monoclonal antibodies. Thus, to further elucidate the mechanistic underpinning of the glucose lowering effects associated with targeting the FGFR1c, we employed whole body positron emission computed tomography (PET/CT) scanning with a glucose tracer (18F-flurodeoxyglucose; 18F-FDG). Given the emphasis on FGF action in adipose in recent publications, we paid particular attention to uptake in white (WAT) and brown (BAT) adipose tissue. Male mice (n=16) received a single subcutaneous injection of vehicle (saline, n=8) or IMC-H7 (3mg/kg, n=8). Group 1 (n=4 per treatment) were transferred to metabolic cages 24 hours post treatment for whole-body metabolic analysis for 48 hours. Group 2 (n=4 per treatment) were assessed for tissue specific glucose uptake via PET/CT. When compared to vehicle controls, mice treated with IMC-H7 exhibited a reduction in body weight (+0.83 ± 0.13 vs -2.97 ± 0.29 g, p < 0.0001) and food intake (4.35 ± 0.44 vs 2.76 ± 0.37 g, p < 0.001). However, there was no effect of treatment on energy expenditure (94.78 ± 10.73 vs 97.50 ± 4.09 kj/kg/hr). Interestingly, PET/CT imaging showed treatment with IMC-H7 significantly increased 18F-FDG uptake in BAT (4.95 ± 0.45 vs 8.24 ± 0.47 SUV, p < 0.01) and WAT (4.16 ± 0.55 vs 6.74 ± 0.79 SUV, p < 0.05), as well as the brain (3.61 ± 0.09 vs 5.24 ± 0.44 SUV, p < 0.01). Whilst 18F-FDG uptake in the quadriceps were significantly reduced in response to treatment with IMC-H7 (2.47 ± 0.12 vs 1.71 ± 0.20 SUV, p < 0.05). This effect, however, was compensated for by the increased glucose uptake in BAT and WAT, as blood glucose was significantly reduced after treatment with IMC-H7 (14.3 ± 0.8 vs 7.5 ± 1.7 mmol/l, p < 0.001). Taken together, these data suggest that antibody-mediated targeting of FGFR1c exerts its powerful glucose-lowering efficacy primarily due to increased glucose uptake in WAT and BAT.