The Fall in Leptin Concentration Is a Major Determinant of the Metabolic Adaptation Induced by Caloric Restriction Independently of the Changes in Leptin Circadian Rhythms

Abstract

Our results confirm an important role for leptin as an independent determinant of the metabolic adaptation in response to CR.

The adaptive metabolic response to exercise-induced weight loss influences both energy expenditure and energy intake

“…In agreement with studies examining dietary-induced weight loss, 11,22,23 the compensatory downregulation in REE observed in the present study was associated with the change in fasting leptin following EX (independent of changes in FM). Baseline fasting leptin concentrations decreased by 13% during EX and this decline was related to the change in FM.…”

Leptin and energy restriction induced adaptation in energy expenditure

“…In addition to these results, the energy restriction induced change in leptin concentration was independently related to the adaptive response, indicating that a greater decrease in leptin correlates with, and could partly explain a greater disproportionate reduction in REE. Previously, leptin had been shown to be correlated to the weight loss induced decrease of REE [43,44]; our results specifically indicate a relation with adaptive thermogenesis, in line with Lecoultre et al [45]. Rosenbaum et al showed that leptin administration during a weight-reduced state returned energy expenditure to pre-weight loss levels [23,24].…”

Drug targeting of leptin resistance

“…It seems that leptin reduction after prolonged caloric restriction is one of those metabolic adaptations, that can be prevented by leptin replacement [124]. In this context, leptin combined with a reduction of caloric intake seems to further maintain weight loss avoiding diet-induced compensatory metabolic adaptations, that induce resistance to weight loss [125]. An optimization of this approach has been to combine leptin administration with other molecules able to improve leptin sensitivity, in order to reinforce body weight loss, the so called "leptin sensitizers".…”