Chemogenetic activation of endogenous arginine vasopressin exerts anorexigenic effects via central nesfatin-1/NucB2 pathway

The Journal of Physiological Sciences - Tập 71 Số 1 - 2021
Kenya Sanada1, Mitsuhiro Yoshimura2, Naofumi Ikeda3, Kazuhiko Baba3, Haruki Nishimura3, Kazuaki Nishimura1, Yuki Nonaka4, Takashi Maruyama1, Tetsu Miyamoto5, Masataka Mori6, Becky Conway-Campbell7, Stafford Lightman7, Masaharu Kataoka5
1Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1–1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807–8555, Japan
2Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS1 3NY, UK. [email protected].
3Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan
4Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
5Second Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
6Research Institute for Metabolism and Obesity, Maebashi, 371-0049, Japan.
7Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS1 3NY, UK.

Tóm tắt

AbstractWe examined whether the chemogenetic activation of endogenous arginine vasopressin (AVP) affects central nesfatin-1/NucB2 neurons, using a transgenic rat line that was previously generated. Saline (1 mL/kg) or clozapine-N-oxide (CNO, 1 mg/mL/kg), an agonist for hM3Dq, was subcutaneously administered in adult male AVP-hM3Dq-mCherry transgenic rats (300–370 g). Food and water intake were significantly suppressed after subcutaneous (s.c.) injection of CNO, with aberrant circadian rhythmicity. The percentages of Fos expression in nesfatin-1/NucB2-immunoreactive neurons were significantly increased in the hypothalamus and brainstem at 120 min after s.c. injection of CNO. Suppressed food intake that was induced by chemogenetic activation of endogenous AVP was ablated after intracerebroventricularly administered nesfatin-1/NucB2-neutralizing antibody in comparison with vehicle, without any alteration of water intake nor circadian rhythmicity. These results suggest that chemogenetic activation of endogenous AVP affects, at least in part, central nesfatin-1/NucB2 neurons and may exert anorexigenic effects in the transgenic rats.

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