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Stomach clusterin as a gut-derived feeding regulator
Cherl Namkoong 1,8,# (Research professor), Bohye Kim 3,4,# (Postdoctoral researcher), Ji Hee Yu 1 (Associate professor), Byung Soo Youn5 (Researcher), Hanbin Kim 3 (Graduate student), Evonne Kim 3 (Graduate student), So Young Gil 1 (Researcher), Gil Myoung Kang 1 (Postdoctoral researcher), Chan Hee Lee 1 (Postdoctoral researcher), Young-Bum Kim 6 (Professor), Kyeong-Han Park 7 (Professor), Min-Seon Kim 1,2 (Professor), Obin Kwon 3,4,* (Assistant Professor)
1Division of Endocrinology and Metabolism, Department of Internal Medicine and 2Asan Institute for Life Sciences, Asan Medical Center and University of Ulsan College of Medicine, Seoul 05505, Korea,
3Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine and 4Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul 03080, Korea,
5Osteoneurogen, Inc., Seoul 08501, Korea,
6Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston MA 02215, USA,
7Department of Anatomy and Cell Biology, Kangwon National University College of Medicine, Chuncheon 24341, Korea,
8Core Research Laboratory, Medical Science Institute, Kyung Hee University Hospital at Gangdong, Seoul 05278, Korea.
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 stomach-specific 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.
Abstract, Accepted Manuscript [Submitted on July 8, 2023, Accepted on September 25, 2023]
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