Effect of Significant Intermediate-term Weight Loss on Serum Leptin Levels and Body Composition in Severely Obese Subjects

Background: Leptin, produced by adipose tissue, signals body fat content to the hypothalamus. Serum leptin levels (SLL), elevated in obese humans, decrease with weight loss. This study investigated the reduction of SLL and fat mass following restrictive bariatric surgery. Methods: Obese subjects (body mass index [BMI] >35 kg/m², n=154) undergoing gastric banding (weight-reduced subjects) were investigated for SLL and body composition before surgery and for 2 years after. Overweight subjects matched for fat mass and gender (fat mass-matched overweight controls, n=194) and subjects who had never been obese (normal weight controls, n=158) were studied for comparison. Results: SLL were highest in weight-reduced subjects and decreased with weight loss (P <0.001), remaining elevated compared with normal weight controls (P <0.001) but lower than fat mass-matched overweight controls (women: P <0.04). At 2 years, SLL normalized for fat mass (allowing comparison between various levels of adiposity) were lower in weight-reduced subjects compared with fat mass-matched overweight controls (women: P =0.003), yet were similar for weight-reduced subjects at 2 years compared with normal weight controls despite 14 kg greater fat mass. Relative lean mass of extremities in weight-reduced subjects increased with weight loss (P <0.001). Conclusion: SLL decreased after considerable weight loss more than could be accounted for by fat mass or BMI reduction alone. This disproportionate decrease in SLL might point to a mechanism that evolved as adaptation to starvation during times of famine. Thus, post-obese subjects may be at risk of weight-regain due to disproportionately low SLL and increased appetite via the leptin-melanocortin pathway.