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

Abstract

Background: Results of leptin administration in mice, rats, and humans provide a rationale for therapeutic augmentation of circulating leptin (OB protein) 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 polyethylene glycol (PEG)-OB protein administration on appetite and energy metabolism in obese men. Design: We performed a randomized, double-blind, placebocontrolled trial in 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 and remained lower in the PEG-OB-protein group, whereas they increased and remained higher in the placebo group (P < 0.0001). During treatment, hunger decreased in the PEG-OB-protein group (P < 0.05) and cognitive restraint increased in the placebo group (P < 0.0001). Neither appetite nor food intake changed significantly during the ad libitum evening meal. Under energy balance conditions in the respiration chamber, appetite at the end of treatment was not significantly different from baseline despite similar, significant reductions 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, or body mass loss relative to placebo treatment, suggesting that PEG-OB protein has central rather than peripheral biological activity in obese men.Am J Clin Nutr 2001;74:426-34.

Fasting leptin and appetite responses induced by a 4-day 65%-energy-restricted diet

“…Furthermore, their study took place in a laboratory setting; participants lived in a metabolic Leptin and appetite responses M Mars et al unit at the time of the study, while the subjects in the present study were free living. Westerterp-Plantenga et al 22 and others found lower hunger and appetite levels in obese male subjects receiving pegylated leptin intravenously than in BMI-and agematched subjects receiving a placebo. 23 Like in the present study, they only observed an effect on appetite while measured in a fasting state.…”

“…11 Up till now, several studies have investigated the association between leptin levels and appetite or food intake in humans, either during conditions of energy balance [14][15][16][17][18][19][20] or energy imbalance. [21][22][23] Especially, the latter studies found evidence for the hypothesis that leptin is involved in the restoration of negative energy balances via appetite. Westerterp-Plantenga et al 22 found a decrease in appetite ratings by administration of exogenous leptin during energy restriction.…”

“…[21][22][23] Especially, the latter studies found evidence for the hypothesis that leptin is involved in the restoration of negative energy balances via appetite. Westerterp-Plantenga et al 22 found a decrease in appetite ratings by administration of exogenous leptin during energy restriction. 22, 23 Keim et al 21 found a strong inverse association between leptin concentrations and appetite ratings during energy restriction, independent of weight loss.…”

“…Westerterp-Plantenga et al 22 found a decrease in appetite ratings by administration of exogenous leptin during energy restriction. 22, 23 Keim et al 21 found a strong inverse association between leptin concentrations and appetite ratings during energy restriction, independent of weight loss. However, both studies were based on several weeks of energy restriction, and did not study the effects of severe energy restriction that take place within days.…”

Effect of dietary restraint during and following pegylated recombinant leptin (PEG-OB) treatment of overweight men

“…16 In a previous study with administration of 20 mg/week pegylated recombinant human leptin, we found that appetite in the postabsorptive state was reduced, but no difference in body mass loss or body composition compared to placebo treatment was demonstrated. 17 In that study, hunger (factor 3, Three-Factor Eating Questionnaire (TFEQ); Stunkard and Messick 18 ) was reduced in the PEG-OB group and cognitive restraint (factor 1, TFEQ) was increased in the placebo group during treatment.…”