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

Objective: Animal studies show that the leptin decline after acute severe caloric restriction is a peripheral signal to increase food intake. However, most human studies have failed to observe such a relationship. We studied the acute effects of severe caloric restriction on the association between serum leptin concentrations and subjective appetite. Subjects: A total of 44 healthy adult men ( aged: 4375 years; BMI: 27.3 +/- 73.2 kg/ m(2)). Measurements: Fasting serum leptin concentrations and self-perceived appetite levels were measured during a 4-day diet containing 36% of the estimated energy requirements. Appetite levels were assessed with a 10-point Likert scale, reflecting hunger, fullness, desire to eat, prospective consumption and total appetite. Results: After the 4-day energy deficit, fasting leptin concentrations decreased by 39.4% (95% Cl: -43.6; -34.9%). This decline was associated with an increase in fasting hunger (r = -0.42; P < 0.01), desire to eat ( r = -0.39; P < 0.05) and total appetite ( r = -0.38; P < 0.05). Furthermore, the association between fasting leptin concentrations and fasting appetite levels became stronger during the energy restriction period ( for total appetite: day 0 r= -0.15, P =0.32; day 2r = -0.31, P = < 0.05; day 4 r = -0.41, P < 0.01). Conclusions: The acute proportional reduction in fasting leptin after 4-day energy restriction is associated with an increase in self-perceived appetite. Additionally, the inverse association between proportional fasting leptin concentrations and self-perceived appetite response becomes stronger as energy restriction is prolonged. These findings suggest that leptin has an instrumental role in restoring energy balance in humans through the expression of appetite.