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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Stomach clusterin as a gut-derived feeding regulator

  • Cherl NamKoong (Appetite Regulation Laboratory, Asan Institute for Life Science, University of Ulsan College of Medicine) ;
  • Bohye Kim (Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine) ;
  • Ji Hee Yu (Division of Endocrinology and Metabolism, Diabetes Center, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Byung Soo Youn (Osteoneurogen, Inc.) ;
  • Hanbin Kim (Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine) ;
  • Evonne Kim (Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine) ;
  • So Young Gil (Appetite Regulation Laboratory, Asan Institute for Life Science, University of Ulsan College of Medicine) ;
  • Gil Myoung Kang (Appetite Regulation Laboratory, Asan Institute for Life Science, University of Ulsan College of Medicine) ;
  • Chan Hee Lee (Appetite Regulation Laboratory, Asan Institute for Life Science, University of Ulsan College of Medicine) ;
  • Young-Bum Kim (Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School) ;
  • Kyeong-Han Park (Department of Anatomy and Cell Biology, Kangwon National University College of Medicine) ;
  • Min-Seon Kim (Appetite Regulation Laboratory, Asan Institute for Life Science, University of Ulsan College of Medicine) ;
  • Obin Kwon (Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine)
  • Received : 2023.07.08
  • Accepted : 2023.09.25
  • Published : 2024.03.31
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Abstract

The stomach has emerged as a crucial endocrine organ in the regulation of feeding since the discovery of ghrelin. Gut-derived hormones, such as ghrelin and cholecystokinin, can act through the vagus nerve. We previously reported the satiety effect of hypothalamic clusterin, but the impact of peripheral clusterin remains unknown. In this study, we administered clusterin intraperitoneally to mice and observed its ability to suppress fasting-driven food intake. Interestingly, we found its synergism with cholecystokinin and antagonism with ghrelin. These effects were accompanied by increased c-fos immunoreactivity in nucleus tractus solitarius, area postrema, and hypothalamic paraventricular nucleus. Notably, truncal vagotomy abolished this response. The stomach expressed clusterin at high levels among the organs, and gastric clusterin was detected in specific enteroendocrine cells and the submucosal plexus. Gastric clusterin expression decreased after fasting but recovered after 2 hours of refeeding. Furthermore, we confirmed that stomachspecific overexpression of clusterin reduced food intake after overnight fasting. These results suggest that gastric clusterin may function as a gut-derived peptide involved in the regulation of feeding through the gut-brain axis.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea funded by the Korean government (2020R1A2C3004843, 2022M3E5E8017213 to M-S.K., 2020R1C1C1008033 to O.K.).

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