The adipocyte-derived hormone adiponectin plays an important role in modulating energy homeostasis through peripheral tissues and the central nervous system. Several studies have reported that adiponectin exists in cerebrospinal fluid and that adiponectin receptors are expressed in the hypothalamus, including the paraventricular nucleus (PVN), which plays a key role in controlling pituitary hormone secretion. Furthermore, it has been reported that magnocellular arginine vasopressin (AVP) neurones within the PVN express adiponectin receptors. These findings suggest a central role of adiponectin in the modulation of neuroendocrinological functions. In the present study, we investigated the effect of centrally-administered adiponectin on AVP release in conscious rats. Intracerebroventricular (i.c.v.) administration of adiponectin significantly reduced the basal plasma AVP concentration in a dose-dependent manner, with a maximal effect being obtained 10min after administration. The plasma AVP increase in response to either hyperosmolar or hypovolaemic stimulation was also significantly attenuated by an i.c.v. injection of adiponectin. Treatment with AMP-activated protein kinase (AMPK) inhibitor compound C (100nmol, i.c.v.) partially reversed the inhibitory effects of adiponectin on AVP release. These findings suggest that central adiponectin plays an inhibitory role in the osmoregulation and baroregulation of AVP release, that the AMPK pathway is at least partly involved in the action of adiponectin, and further suggest a novel physiological or pathophysiological role for central adiponectin in water balance via inhibition of AVP release.
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