Effects of intracerebroventricular injection of nesfatin‐1 on autonomic nerve activities in rats and mice

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Nesfatin‐1, one of neuropeptides, reduces appetite and enhances energy expenditure in animals. Previous our experiment showed that intracerebroventricular (ICV) administration of nesfatin‐1 suppressed food intake and stimulated sympathetic nerve outflows to the kidney and the white adipose tissue through the hypothalamic ERK signals (Tanida M., et al., Diabetes 2015). However, it has not been examined whether central nesfatin‐1 affects efferent sympathetic nerve activities to the adrenal gland or the brown adipose tissue regulating cardiovascular function or thermogenesis, respectively, and efferent vagal nerve outflow. Here, we investigated effects of ICV injection of nesfatin‐1 on efferent adrenal sympathetic nerve activity (ASNA) and brown adipose tissue sympathetic nerve activity (BAT‐SNA), and efferent gastric vagal nerve activity (GVNA) in anesthetized rats. In addition, to check species difference in nesfatin‐1 action on autonomic nerves, sympathetic response to ICV injection of nesfatin‐1 was determined in anesthetized mice.Electrophysiological recordings of autonomic nerve activities in anesthetized rats and mice were performed within the scope of our previous studies (Tanida M., et al., Diabetes 2015, Tanida M., Neuroscience 2013). All animal care and handling procedures were approved by the Animal Research Committees of Kanazawa Medical University. 7–10days after ICV surgery, rats and mice were anesthetized with intraperitoneal injections of a urethane (750 mg/kg) and a‐chloralose (75 mg/kg) mixture. ASNA, BAT‐SNA and GVNA in rats, and sympathetic nerve to the kidney in mice were measured by electrophysiological system.In the present study, we found that ICV injection of nesfatin‐1 (20, 200 pmol) activated ASNA and BAT‐SNA in dose‐dependent manner while the GVNA was suppressed by nesfatin‐1. In addition, pretreatment with the melanocortin‐3/4 receptor antagonist, SHU9119, attenuated the increase in ASNA induced by nesfatin‐1. These data suggest that hypothalamic nesfatin‐1 stimulates not only renal sympathetic nerve but also sympathetic nerve activities to the adrenal gland and the brown adipose tissue via the hypothalamic melanocortin system to regulate cardiovascular and thermogenic actions. Similar with sympathetic responses of rats to nesfatin‐1, nesfatin‐1 injection to the mice also activated renal sympathetic outflow, indicating that sympathoexcitation of the kidney was also induced in mice.