Digestive and metabolic processes are entrained by restricted feeding (RFS) schedules and are thought to be potential elements of a food-entrained oscillator (FEO). Due to the close relationship of leptin with metabolic regulation and because leptin is a relevant communication signal of the individual's peripheral metabolic condition with the central nervous system, we explored whether leptin is an endogenous entraining signal from the periphery to a central element of an FEO. First we characterized in the rat the diurnal rhythm of serum leptin (in rats fed ad libitum (AL)), its adjustment to an RFS and the influence of fasting after RFS, or RFS followed by AL feeding and then total food deprivation (RF-AF) in the persistence of this fluctuating pattern. We also explored the response of free fatty acids and stomach weight under the same entraining conditions. We compared the metabolic response with the behavioral expression of drinking anticipatory activity (AA) under the same conditions. Finally, we tested the effect of daily i.c.v administration of leptin as a putative entraining signal for the generation of AA.Metabolic parameters responded to food entrainment by adjusting their phase to mealtime. However, leptin and free fatty acid rhythms persisted only for a few cycles in fasting conditions and readjusted to the light-darkness cycle after an RF-AF protocol. In contrast, behavioral food-entrained rhythms persisted after both fasting manipulations. Daily leptin i.c.v. administration did not produce AA, nor produce changes in the behavioral free-running rhythm. Stomach weight indicated an adaptive process allowing an extreme stomach distension followed by a slow emptying process, which suggests that the stomach may be playing a relevant role as a storage organ. In conclusion, metabolic signals here studied respond to feeding schedules by adjusting their phase to mealtime, but do only persist for a few cycles in fasting. Leptin does not produce AA and thus is not an entraining signal for FEO. The response of metabolic signals to feeding schedules depends on different mechanisms than the expression of AA.

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