Key result
Microinjection of the MC3/4R agonist melanotan II into the paraventricular nucleus dose-dependently enhanced the adipose afferent reflex, an effect mediated by the cAMP-PKA signaling pathway.
p-value: p=<0.05
Activation of MC4Rs in the paraventricular nucleus enhances the adipose afferent reflex via a cAMP-PKA signaling pathway in rats.
No immediate clinical implications; leaves open translation of PVN MC4R-cAMP-PKA effects on adipose reflex to humans.
BACKGROUND AND AIM: Paraventricular nucleus (PVN) of hypothalamus is an important central component in modulating adipose afferent reflex (AAR). Melanocortin receptors (MC3/4Rs) expressions are found in the hypothalamic PVN. This study was designed to determine the roles of MC3/4Rs in the PVN in modulating the AAR and its downstream signaling pathway in normal rats. METHODOLOGY/PRINCIPAL FINDINGS: Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats. AAR was evaluated using RSNA and MAP responses to capsaicin injection into the inguinal white adipose tissue (iWAT). Microinjection of the MC3/4R agonist melanotan II (MTII) into the PVN enhanced the AAR. The MC3/4R antagonist SHU9119 or MC4R antagonist HS024 attenuated the AAR and abolished MTII-induced AAR response. The adenylate cyclase (AC) inhibitor SQ22536 or the protein kinase A (PKA) inhibitor Rp-cAMP attenuated the AAR and the effect of MTII on the AAR was abolished by pretreatment with SQ22536 or Rp-cAMP in the PVN. Furthermore, both PVN microinjection of MTII and iWAT injection of capsaicin increased the cAMP level in the PVN. SHU9119 in the PVN abolished the increase in cAMP level which induced by iWAT injection of capsaicin. CONCLUSION: The activation of MC4Rs rather than MC3Rs enhances the AAR, and a cAMP-PKA pathway is involved in the effects of MC4Rs in the PVN.
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Li et al. (2013) studied Normal physiological state (Adipose Afferent Reflex). Melanotan II (MTII) vs. Saline was evaluated on Adipose afferent reflex (AAR) evaluated by renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to capsaicin injection (p=<0.05). Microinjection of the MC3/4R agonist melanotan II into the paraventricular nucleus dose-dependently enhanced the adipose afferent reflex, an effect mediated by the cAMP-PKA signaling pathway.
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