Adiponectin selectively inhibits oxytocin neurons of the paraventricular nucleus of the hypothalamus

Abstract

Adiponectin is an adipocyte derived hormone which acts in the brain to modulate energy homeostasis and autonomic function. The paraventricular nucleus of the hypothalamus (PVN) which plays a key role in controlling pituitary hormone secretion has been suggested to be a central target for adiponectin actions. A number of hormones produced by PVN neurons have been implicated in the regulation of energy homeostasis including oxytocin, corticotropin releasing hormone and thyrotropin releasing hormone. In the present study we investigated the role of adiponectin in controlling the excitability of magnocellular (MNC -oxytocin or vasopressin secreting) neurons within the PVN. Using RT-PCR techniques we have shown expression of both adiponectin receptors in the PVN. Patch clamp recordings from MNC neurons in hypothalamic slices have also identified mixed (27% hyperpolarization, 42% depolarization) effects of adiponectin in modulating the excitability of the majority of MNC neurons tested. These effects are maintained when cells are placed in synaptic isolation using tetrodotoxin. Additionally we combined electrophysiological recordings with single cell RT-PCR to examine the actions of adiponectin on MNC neurons which expressed oxytocin only, vasopressin only, or both oxytocin and vasopressin mRNA and assess the profile of receptor expression in these subgroups. Adiponectin was found to hyperpolarize 100% of oxytocin neurons tested (n = 6), while vasopressin cells, while all affected (n = 6), showed mixed responses. Further analysis indicates oxytocin neurons express both receptors (6/7) while vasopressin neurons express either both receptors (3/8) or one receptor (5/8). In contrast 6/6 oxytocin/vasopressin neurons were unaffected by adiponectin. Co-expressing oxytocin and vasopressin neurons express neither receptor (4/6). The results presented in this study suggest that adiponectin plays specific roles in controlling the excitability oxytocin secreting neurons, actions which correlate with the current literature showing increased oxytocin secretion in the obese population.

The paraventricular nucleus of the hypothalamus – a potential target for integrative treatment of autonomic dysfunction

“…Treatment with ADP lowers hepatic gluconeogenesis, serum glucose and ameliorates insulin resistance in mice [40][41][42][43]. Recent studies demonstrating that microinjection of ADP into the cerebral ventricles of mice also caused changes in glucose, lipid handling, and body weight have identified the brain and the PVN in particular as a potentially important target for ADP actions [44].Two different adiponectin receptors have been identified, adipoR1 and adipoR2 [40], and we have confirmed expression of adiponectin receptors in the PVN and also have identified direct hyperpolarizing effects of adiponectin on magnocellular oxytocin secreting neurons in the PVN, cells which also express mRNA for both adiponectin receptors (shown using single cell RTPCR) [45]. In contrast, we have also obtained preliminary data showing depolarizing effects of adiponectin on parvocellular CRH and TRH neurons in hypothalamic slices (again identified using single cell RTPCR) and have correlated these observations with data from conscious animals showing that intracerebroventricular adiponectin also increases plasma ACTH concentrations (Hoyda et al -unpublished).…”

Adiponectin action from head to toe

“…AdipoR1 and AdipoR2 receptors are widely distributed throughout the central nervous system (CNS), with expression detected in regions of the hypothalamus and brainstem that are involved in the control of feeding behavior and energy expenditure [181,182,187]. Moreover, it was recently demonstrated that adiponectin can influence the excitability of different groups of neuron in the paraventricular nucleus, including neuroendocrine-CRH, preautonomic-TRH and preautonomic-oxytocin neurons [188].…”

Expression of Adiponectin and Adiponectin Receptors in Human Pituitary Gland and Brain

“…area postrema and paraventricular nuclei neurons [11, 14, 27, 28] and murine brain endothelial cells [15], as well as in human brain whole extracts [11, 19]. Furthermore, adiponectin receptor mRNA has been documented in rat and human pituitary extracts [23, 26].…”