Stomach clusterin as a gut-derived feeding regulator

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 periphe...

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Published inBMB reports Vol. 57; no. 3; p. 149
Main Authors NamKoong, Cherl, Kim, Bohye, Yu, Ji Hee, Youn, Byung Soo, Kim, Hanbin, Kim, Evonne, Gil, So Young, Kang, Gil Myoung, Lee, Chan Hee, Kim, Young-Bum, Park, Kyeong-Han, Kim, Min-Seon, Kwon, Obin
Format Journal Article
LanguageEnglish
Published Korea (South) 01.03.2024
Subjects
Animals
Cholecystokinin - pharmacology
Clusterin - pharmacology
Eating - physiology
Feeding Behavior
Ghrelin - pharmacology
Mice
Stomach
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Summary: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. [BMB Reports 2024; 57(3): 149-154].
ISSN:1976-670X
DOI:10.5483/BMBRep.2023-0117