Innervation of skeletal muscle by leptin receptor-containing neurons

In addition to suppressing food intake, leptin reduces body adiposity by altering metabolism within peripheral tissues such as adipose tissue and muscle. Recent work indicates that leptin action within the brain is sufficient to promote glucose uptake and increase fat oxidation within skeletal muscle, and that these effects are dependent on the sympathetic nervous system. To identify neuronal circuits through which leptin impacts skeletal muscle metabolism, we used LepRb-GFP reporter mice in combination with muscle-specific injection of an mRFP-expressing pseudorabies virus (PRV), which acts as a transsynaptic retrograde tracer. Consistent with previous observations in the rat, muscle-specific PRV injection lead to labeling within multiple areas of the hypothalamus and brainstem. However, the only areas in which PRV and LepRb colocalization was detected were within the brainstem nucleus of the solitary tract (NTS) and the hypothalamic retrochiasmatic area. Within the NTS 28.5+/-9.4% of PRV-positive neurons contained LepRb-GFP, while in the RCH 37+/-1.7% of PRV neurons also contained LepRb. In summary, these data clearly implicate the NTS and RCH as key sites through which brain leptin impacts skeletal muscle, and as such provide an anatomical framework within which to interpret physiological data indicating that leptin acts in the brain to influence metabolism within skeletal muscle.