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J Physiol Sci. 2021 Jun 16;71(1):18. doi: 10.1186/s12576-021-00802-4.

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

The journal of physiological sciences : JPS

Kenya Sanada, Mitsuhiro Yoshimura, Naofumi Ikeda, Kazuhiko Baba, Haruki Nishimura, Kazuaki Nishimura, Yuki Nonaka, Takashi Maruyama, Tetsu Miyamoto, Masatomo Mori, Becky Conway-Campbell, Stafford Lightman, Masaharu Kataoka, Yoichi Ueta

Affiliations

  1. Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
  2. Second Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
  3. Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan. [email protected].
  4. Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS1 3NY, UK. [email protected].
  5. Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
  6. Research Institute for Metabolism and Obesity, Maebashi, 371-0049, Japan.
  7. Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS1 3NY, UK.
  8. Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan. [email protected].

PMID: 34134629 DOI: 10.1186/s12576-021-00802-4

Abstract

We 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.

Keywords: Arginine vasopressin; DREADDs; Feeding; Hypothalamus; Nesfatin-1/NucB2; Transgenic rat

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