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The effect of acute resistance exercise (RE) on whole body energy expenditure (EE) and α2-adrenergic receptor (α2-AR) regulation of lipolysis in subcutaneous abdominal adipose tissue (SCAAT) was determined in sedentary lean (LN) and obese (OB) men. Lipolysis was monitored using microdialysis in 10 LN [body mass index (BMI) 20.9 ± 0.6] and 10 OB (BMI 36.2 ± 2.7) men before, during, and for 24 h after RE. EE was measured before and immediately after RE for 40 min. Changes in interstitial glycerol were measured in SCAAT with three microdialysis probes perfused with a control solution, phentolamine (α2-AR antagonist), or propranolol (β-AR antagonist). EE and fat oxidation (FOX) were significantly ( P < 0.001) elevated immediately post-RE compared with pre-RE in LN and OB subjects, with no differences between groups. RE-induced increases in SCAAT glycerol concentrations from rest to peak exercise were greater in LN than in OB men in the control (LN 142.1 ± 30.8 vs. OB 65.4 ± 14.2%, P = 0.03) and phentolamine probes (LN 187.2 ± 29.6 vs. OB 66.7 ± 11.0%, P = 0.002). Perfusion of propranolol had no effect on interstitial glycerol concentrations over the time course of the experiment in either group. Plasma insulin concentrations were significantly lower ( P = 0.002) and plasma growth hormone (GH) was significantly higher ( P = 0.03) in LN compared with OB men. The mechanism behind RE contributing to improved body composition may in part be due to enhanced SCAAT lipolysis and improved EE and FOX in response to RE in LN and OB men. The blunted SCAAT lipolytic response to RE in OB compared with LN men is unrelated to RE-induced catecholamine activation of the antilipolytic α2-ARs and may be due to depressed GH in OB subjects.