Leptin reverses declines in satiation in weight-reduced obese humans

Abstract

Background: Individuals who are weight-reduced or leptin deficient have a lower energy expenditure coupled with higher hunger and disinhibition and/or delayed satiation compared with never-weight-reduced control subjects. Because exogenous leptin inhibits feeding in congenitally leptin-deficient humans, reduced leptin signaling may reduce the expression of feeding inhibition in humans.

Objective: The objective was to test the hypothesis that reduced leptin signaling may reduce the expression of feeding inhibition (ie, blunt satiation) in humans by examining the effects of leptin repletion on feeding behavior after weight loss.

Design: Ten obese humans (4 men, 6 women) were studied as inpatients while they received a weight-maintaining liquid-formula diet. Satiation was studied by measuring intake and ratings of appetite-related dispositions 3 h after ingestion of 300 kcal of the liquid-formula diet. The subjects were studied at each of 3 time periods: 1) while they maintained their usual weight (Wt(initial)) and then after weight reduction and stabilization at 10% below initial weight and while they received 5 wk of either 2) twice-daily injections of placebo (Wt(-10%placebo)) or 3) "replacement doses" of leptin (Wt(-10%leptin)) in a single-blind crossover design with a 2-wk washout period between treatments. Energy expenditure was also measured at each study period.

Results: Both energy expenditure and visual analog scale ratings that reflect satiation were significantly lower at Wt(-10%placebo) than at Wt(initial) and Wt(-10%leptin).

Conclusion: The results are consistent with the hypothesis that the absence of leptin signaling after weight loss may blunt the expression of feeding inhibition in humans.

FIGURE 1.

Schematic of protocol. Subjects were studied after stabilization at usual weight during a liquid-formula diet. They were then placed on a liquid-formula diet (800 kcal/d) until they had lost ∼10% of Wt_initial and were stabilized at that weight. Once weight was stable, subjects were randomly assigned in a single-blind crossover design to receive twice daily injections of either a placebo or leptin for 5 wk with a 2-wk washout period between treatments. Subjects were studied again at the end of Wt_-10%placebo and Wt_-10%leptin, ie, while still receiving leptin or placebo injections. Leptin doses were calculated and titrated to restore circulating leptin concentrations at 0800 to pre–weight-loss concentrations. Subjects were inpatients throughout the study. Wt_initial, usual weight was maintained; Wt_-10%leptin, after weight reduction and stabilization at 10% below initial weight and while subjects received twice-daily injections of leptin; Wt_-10%placebo, after weight reduction and stabilization at 10% below initial weight and while subjects received twice-daily injections of placebo.