• energy expenditure
• fasting
• leptin
• overfeeding

Circulating levels of leptin may play a role in the central regulation of energy expenditure (EE) and maintenance of body weight. Acute negative changes in energy balance such as 24 hours of fasting induce decreases in both leptin levels and EE. On the other hand, positive changes during overfeeding dietary different interventions cause increases in leptin levels and EE. In our recent studies, a greater decrease in EE during fasting predicted less weight loss under caloric restriction and weight gain in free-living conditions. The physiologic underpinnings of the changes in EE are not known but, as leptin changes also with negative or positive energy balance, it is a good candidate for mediating decrease in EE and influencing future weight gain.
Fifty-nine healthy subjects (48 men, age: 37±10 y, body fat by DXA: 28±10%) with normal glucose regulation were admitted to our clinical research unit to measure 24h-EE and RQ within a whole room indirect calorimeter during a standard diet in energy balance (EB), 24h fasting (FST) and five different overfeeding diets. Leptin plasma concentrations were measured in the morning prior to and after FST and five different dietary interventions. The percentage change in 24h-EE (%EE) was calculated as the difference divided by the 24h-EE during EB. Follow-up data of weight change were available for 45 subjects after 6 months.
As compared to EB, %EE decreased during FST (−7.3±4.4%, p<0.0001). Leptin levels also decrease by 67% after FST (pre-FST: 15.1±19.6 ng/mL, post-FST: 5.0±8.1; Δ=−10±12.8, p<0.001) but the individual reduction in leptin did not correlate with %EE (r=0.12, p=0.39) or RQ (r=0.14, p=0.28). No correlations between 24-h EE and leptin change (%) were observed in others dietary interventions (all p > 0.24). Furthermore, percent reduction in leptin during FST did not predict weight change at 6 months (p=0.77) and no correlation were observed between the change in body weight and the leptin change (%) during the five overfeeding diets (all p value > 0.3)
Although leptin and EE both decrease during fasting and both increase during overfeeding, the reduction/increase in leptin levels was not associated with the concomitant decline/raise in EE or with subsequent weight change. These results indicate that leptin may not play a major role in the metabolic adaptation to caloric restriction and overfeeding that influences body weight change or at least is a ‘complementary’ hormone, with others appetite hormones, to mediate that process.