Leptin acts as a feedback signal to the hypothalamus to decrease appetite and increase metabolic rate as adipose tissue accumulates. Administration of leptin to ob/ob leptin deficient mice causes dramatic reductions in body weight. From these results it was hoped that administration of leptin would cause rapid weight loss in obese humans. Although this was the case with overweight humans that were deficient in leptin (like the ob/ob mice), trials using leptin on overweight leptin-sufficient humans were disappointing, leading to speculation that a defective or down-regulated leptin receptor may be the cause of the obesity. If obese individuals are insensitive to leptin, falls in leptin following rapid weight loss may be particularly problematic for obese individuals. Such individuals may be particularly sensitive to reductions in circulating leptin due to adipose tissue loss, which may decrease satiety and metabolic rate causing rapid weight regain.
Researchers1 have administered leptin to 10 obese subjects following weight loss, in order to assess the effects on hunger and energy expenditure. Subjects were studied before weight loss, following a 10% reduction caused by a liquid diet formula, and while they received either leptin or placebo for 5 weeks. A wash out period of two weeks was followed by subjects switching to the opposite treatment. Satiety was taken by measuring a subjective rating following consumption of 300 kcal of their liquid formula meal. Treatment with leptin significantly increased energy expenditure and improved satiation compared to the placebo. Subjects also had improved satiety at baseline before weight loss when compared to following weight loss, but only if in the placebo group. These results suggest that leptin administration to obese subjects following weight loss might improve metabolic rate and decrease hunger.
The main problem surrounding weight loss is the high failure rate, and this is concerning. Recidivism following successful weight loss may be as high as 75 to 90%. The findings of this study suggest that the hyperphagia and hypometabolic rate may be related to the rapid reduction in the adiposity of the subjects. Administration of leptin may trick the body into believing that adipose levels are still high and therefore maintain higher levels of satiety and rates of metabolism. This may also explain the success of longer-term slower weight loss over rapid weight loss, the latter being more significantly associated with recidivism. Leptin repletion following weight loss may therefore be a successful strategy to allow more effective maintenance of the lower body weight. However, although satiety and metabolic rate were improved in this study, the effects on body weight remain unknown.
RdB
