Identification of Leptin Receptor-Expressing Cells in the Nodose Ganglion of Male Mice

• Published in: Endocrinology (Philadelphia) 2019-05, Vol.160 (5), p.1307-1322
• Main Authors: Leon Mercado, Luis, Caron, Alexandre, Wang, Yibing, Burton, Michael, Gautron, Laurent
• Format: Article
• Language: English
• Subjects: Angiotensin AT1 receptors; Angiotensins; Animal models; Animals; Baroreceptors; Cells, Cultured; Endocrinology; Fibers; Ganglion cells; Ganglion cysts; Gene Expression - drug effects; Genes; Health aspects; Hormone receptors; Hybridization; Identification and classification; Identity; In Situ Hybridization - methods; Leptin; Leptin - administration & dosage; Leptin - pharmacology; Male; Messenger RNA; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; mRNA; NAV1.8 Voltage-Gated Sodium Channel - genetics; NAV1.8 Voltage-Gated Sodium Channel - metabolism; Neurons; Neurons - drug effects; Neurons - metabolism; Neurons, Afferent - metabolism; Nodose ganglion; Nodose Ganglion - cytology; Nodose Ganglion - drug effects; Nodose Ganglion - metabolism; Parenchyma; Peritoneum; Physiological aspects; Polymerase chain reaction; Receptors, Leptin - genetics; Receptors, Leptin - metabolism; RNA; Sodium channels (voltage-gated); Vagus nerve; Vagus Nerve - cytology; Vagus Nerve - metabolism
• ISSN: 1945-7170; 0013-7227; 1945-7170
• DOI: 10.1210/en.2019-00021

Leptin has been proposed to modulate viscerosensory information directly at the level of vagal afferents. In support of this view, broad expression for the leptin receptor (Lepr) has previously been reported in vagal afferents. However, the exact identity and distribution of leptin-sensitive vagal afferents has not been elucidated. Using quantitative PCR, we found that the whole mouse nodose ganglion was predominantly enriched in the short form of Lepr, rather than its long form. Consistent with this observation, the acute administration of leptin did not stimulate JAK-STAT signaling in the nodose ganglion. Using chromogenic in situ hybridization in wild-type mice and several reporter mouse models, we demonstrated that Lepr mRNA was restricted to nonneuronal cells in the epineurium and parenchyma of the nodose ganglion and a subset of vagal afferents, which accounted for only 3% of all neuronal profiles. Double labeling studies further established that Lepr-expressing vagal afferents were Nav1.8-negative fibers that did not supply the peritoneal cavity. Finally, double chromogenic in situ hybridization revealed that many Lepr-expressing neurons coexpressed the angiotensin 1a receptor (At1ar), which is a gene expressed in baroreceptors. Taken together, our data challenge the commonly held view that Lepr is broadly expressed in vagal afferents. Instead, our data suggest that leptin may exert a previously unrecognized role, mainly via its short form, as a direct modulator of a very small group of At1ar-positive vagal fibers.