Effects of weekly administration of pegylated recombinant human OB proteinon appetite profile and energy metabolism in obese men

Background: Results of leptin administration in mice, rats, and humans prov ide a rationale for therapeutic augmentation of circulating leptin (OB prot ein) concentrations in obese humans; this may reduce food intake, increase metabolic rate, and lower body mass. Objective: We assessed the effects of weekly subcutaneous pegylated polyeth ylene glycol (PEG)-OB protein administration on appetite and energy metabol ism in obese men. Design: We performed a randomized, double-blind, placebo-controlled trial i n 30 obese men [body mass index (in kg/m(2)): 34.2 +/-3.6; age: 44.7 +/-7 y ]. Subjects received 20 mg PEG-OB protein/wk for 12 wk while limiting their energy intake to 2.1 MJ/d. Results: During treatment, appetite and hunger before breakfast decreased a nd remained lower in the PEG-OB-protein group, whereas they increased and r emained higher in the placebo group (P<0.0001). During treatment, hunger de creased in the PEG-OB-protein group (P<0.05) and cognitive restraint increa sed in the placebo group (P<0.0001). Neither appetite nor food intake chang ed significantly during the ad libitum evening meal. Under energy balance c onditions in the respiration chamber, appetite at the end of treatment was not significantly different from baseline despite similar, significant redu ctions in 24-h energy intake, energy expenditure, sleeping metabolic rate, body mass, fat mass, and fat-free mass (P<0.01 for all) in both groups. Conclusion: Treatment with PEG-OB protein modified subjective appetite at a dosage that produced no changes in body composition, energy expenditure, o r body mass loss relative to placebo treatment, suggesting that PEG-OB prot ein has central rather than peripheral biological activity in obese men.