title: Hypothalamic Nesfatin-1 Stimulates Sympathetic Nerve Activity via Hypothalamic ERK Signaling.
abstract: Nesfatin-1 acts on the hypothalamus and regulates the autonomic nervous system. However, the hypothalamic mechanisms of nesfatin-1 on the autonomic nervous system are not well understood. In this study, we found that intracerebroventricular (ICV) administration of nesfatin-1 increased the extracellular signal-regulated kinase (ERK) activity in rats. Furthermore, the activity of sympathetic nerves, in the kidneys, liver, and white adipose tissue (WAT), and blood pressure was stimulated by the ICV injection of nesfatin-1, and these effects were abolished owing to pharmacological inhibition of ERK. Renal sympathoexcitatory and hypertensive effects were also observed with nesfatin-1 microinjection into the paraventricular hypothalamic nucleus (PVN). Moreover, nesfatin-1 increased the number of phospho (p)-ERK1/2-positive neurons in the PVN and coexpression of the protein in neurons expressing corticotropin-releasing hormone (CRH). Pharmacological blockade of CRH signaling inhibited renal sympathetic and hypertensive responses to nesfatin-1. Finally, sympathetic stimulation of WAT and increased p-ERK1/2 levels in response to nesfatin-1 were preserved in obese animals such as rats that were fed a high-fat diet and leptin receptor-deficient Zucker fatty rats. These findings indicate that nesfatin-1 regulates the autonomic nervous system through ERK signaling in PVN-CRH neurons to maintain cardiovascular function and that the antiobesity effect of nesfatin-1 is mediated by hypothalamic ERK-dependent sympathoexcitation in obese animals.
authors: Department of Physiology II, Kanazawa Medical University, Uchinada, Ishikawa, Japan mtanida@kanazawa-med.ac.jp.
authors: Mamoru
authors: M
authors: Tanida
authors: Department of Biology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Hitoshi
authors: H
authors: Gotoh
authors: College of Pharmacology, Hokuriku University, Kanazawa, Ishikawa, Japan.
authors: Naoki
authors: N
authors: Yamamoto
authors: Department of Physiology II, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
authors: Mofei
authors: M
authors: Wang
authors: Department of Physiology II, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
authors: Yuhichi
authors: Y
authors: Kuda
authors: Department of Physiology II, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
authors: Yasutaka
authors: Y
authors: Kurata
authors: Kitakanto Molecular Novel Research Institute for Obesity and Metabolism, Midori City, Gunma, Japan.
authors: Masatomo
authors: M
authors: Mori
authors: Department of Physiology II, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
authors: Toshishige
authors: T
authors: Shibamoto
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects / Q000294:innervation; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D059305:Diet, High-Fat; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D008099:Liver / Q000187:drug effects / Q000294:innervation; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D000080866:Nucleobindins; D010766:Phosphorylation; D051381:Rats; D011924:Rats, Zucker; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins