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- Title
Hypothalamic Nesfatin-1 Stimulates Sympathetic Nerve Activity via Hypothalamic ERK Signaling.
- Authors
Mamoru Tanida; Hitoshi Gotoh; Naoki Yamamoto; Mofei Wang; Yuhichi Kuda; Yasutaka Kurata; Masatomo Mori; Toshishige Shibamoto; Tanida, Mamoru; Gotoh, Hitoshi; Yamamoto, Naoki; Wang, Mofei; Kuda, Yuhichi; Kurata, Yasutaka; Mori, Masatomo; Shibamoto, Toshishige
- 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.
- Subjects
HYPOTHALAMIC hormones; SYMPATHETIC nervous system; HYPOTHALAMUS; AUTONOMIC nervous system; CORTICOTROPIN releasing hormone; OBESITY; PROTEIN expression; KIDNEY innervation; ADIPOSE tissues; ANIMAL experimentation; BLOOD pressure; CALCIUM-binding proteins; CELLULAR signal transduction; DIET; KIDNEYS; LIVER; NERVE tissue proteins; NEURONS; PHOSPHORYLATION; RATS; DNA-binding proteins; INNERVATION
- Publication
Diabetes, 2015, Vol 64, Issue 11, p3725
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db15-0282