Abstract

Leptin resistance is associated with impaired respiratory function, obesity related respiratory disorders, and a higher incidence of respiratory illness in children of obese mothers. There have been few attempts to identify its site of action in respiratory centers of the brain and no studies on its respiratory effects in neonates. We hypothesize that the direct effect of leptin on the respiratory system is inhibitory, as it is in other brain regions, but that effects on metabolism may override this inhibition in the whole animal. We performed experiments on neonatal rat pups, postnatal day 0 to 6. Bath application of 300nM leptin to four brainstem spinal cord (BSSC) preparations had varied effects on burst amplitude and frequency of Cervical 4 ventral roots (C4VR). In three split bath BSSC preparations, 100uL of 0.5mg/ml leptin applied to the medullary compartment slowed or abolished C4VR rhythm, which recovered with washout. Whole bath application of 300nM leptin to five rhythmic medullary slices abolished hypoglossal rootlet rhythm, which recovered with washout. Microinjections of 0.5 mg/ml leptin, but not vehicle injection, into the pre‐Botzinger complex of two BSSC preps slowed or abolished C4VR rhythm. These preliminary results suggest that leptin receptors are located on pre‐Botzinger complex cells, and that leptin’s action is inhibitory.Grant Funding Source: Supported by ROIHD071302

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