Effects of intermittent hypoxia on leptin signalling in the carotid body

Role of the Carotid Body in Obesity-Related Sympathoactivation

“…Hyperleptinemia and chronic intermittent hypoxia may be inter-related mechanisms of sympathoactivation through peripheral chemoreceptors because chronic intermittent hypoxia increases plasma leptin levels and leptin immunoreactivity in the carotid body. 4,5 In conclusion, the carotid body may potentially participate in sympathoactivation of obesity through increased chemosensitivity because of chronic intermittent hypoxia or the direct action of leptin. Thus, the carotid body also may be viewed as a therapeutic target for obesity-related sympathoactivation, although further experimental and clinical data are certainly needed.…”

“…However, leptin and leptin receptors also have recently been identified in human and rat glomus cells, 3 and intravenous injections of leptin have been reported to increase Fos, Fra-1/2, and extracellular signal-regulated kinase 1/2 immunoreactivity in glomus cells, indicating cell activation. 4,5 Immunoreactivity for the long form of the leptin receptor has also been found in vagal nerve and carotid sinus nerve fibers, together with afferent neurons of the petrosal and nodose ganglia. Increased expression of Fos and Fra-1/2 has also been observed in these neurons in response to leptin infusion.…”

Leptin dependent changes in the expression of tropomyosin receptor kinase B protein in nucleus of the solitary tract to acute intermittent hypoxia

“…All experimental procedures were done in accordance with the guidelines on the use and care of laboratory animals as set by the Canadian Council on Animal Care and approved by the Animal Care Committee at The University of Western Ontario. Animals were exposed on the day of the study (0900-1700 h) to IH or normoxia conditions as previously described [35,36,40]. Immediately following exposure to IH or normoxia, animals were sacrificed under equithesin anesthesia (0.3 ml/100 g body weight) [35,36] and the brains removed and quickly frozen at −80 • C until analyzed.…”

“…Animals were exposed on the day of the study (0900-1700 h) to IH or normoxia conditions as previously described [35,36,40]. Immediately following exposure to IH or normoxia, animals were sacrificed under equithesin anesthesia (0.3 ml/100 g body weight) [35,36] and the brains removed and quickly frozen at −80 • C until analyzed. Frozen serial brain sections were cut at 500 m in a cryostat and an 800 m diameter micropunch was taken of the caudal medial NTS, bilaterally.…”

“…These receptors then transmit the increased afferent neural activity to the caudal medial nucleus of the solitary tract (NTS), including the commissural and medial subnuclei of the NTS complex, the primary site of peripheral chemoreceptor afferent termination [10]. In addition, during each acute exposure to IH the leptin levels within the circulation have been shown to be elevated [35,36,40]. Changes in circulatory levels of leptin have been reported to not only exacerbate the effects of chemoreceptor reflex activation on the cardiovascular system, but also potentiate the neuronal responses in NTS to chemoreflex activation [12] while inhibiting the neuronal responses to baroreflex activation [9].…”