Stomach clusterin as a gut-derived feeding regulator
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The stomach has emerged as a crucial endocrine organ in theregulation of feeding since the discovery of ghrelin. Gut-derivedhormones, such as ghrelin and cholecystokinin, can act throughthe vagus nerve. We previously reported the satiety effect ofhypothalamic clusterin, but the impact of peripheral clusterinremains unknown. In this study, we administered clusterinintraperitoneally to mice and observed its ability to suppressfasting-driven food intake. Interestingly, we found its synergismwith cholecystokinin and antagonism with ghrelin. These effectswere accompanied by increased c-fos immunoreactivity innucleus tractus solitarius, area postrema, and hypothalamicparaventricular nucleus. Notably, truncal vagotomy abolishedthis response. The stomach expressed clusterin at high levelsamong the organs, and gastric clusterin was detected in specificenteroendocrine cells and the submucosal plexus. Gastricclusterin expression decreased after fasting but recovered after2 hours of refeeding. Furthermore, we confirmed that stomachspecificoverexpression of clusterin reduced food intake afterovernight fasting. These results suggest that gastric clusterinmay function as a gut-derived peptide involved in the regulationof feeding through the gut-brain axis.
Abstract
The stomach has emerged as a crucial endocrine organ in theregulation of feeding since the discovery of ghrelin. Gut-derivedhormones, such as ghrelin and cholecystokinin, can act throughthe vagus nerve. We previously reported the satiety effect ofhypothalamic clusterin, but the impact of peripheral clusterinremains unknown. In this study, we administered clusterinintraperitoneally to mice and observed its ability to suppressfasting-driven food intake. Interestingly, we found its synergismwith cholecystokinin and antagonism with ghrelin. These effectswere accompanied by increased c-fos immunoreactivity innucleus tractus solitarius, area postrema, and hypothalamicparaventricular nucleus. Notably, truncal vagotomy abolishedthis response. The stomach expressed clusterin at high levelsamong the organs, and gastric clusterin was detected in specificenteroendocrine cells and the submucosal plexus. Gastricclusterin expression decreased after fasting but recovered after2 hours of refeeding. Furthermore, we confirmed that stomachspecificoverexpression of clusterin reduced food intake afterovernight fasting. These results suggest that gastric clusterinmay function as a gut-derived peptide involved in the regulationof feeding through the gut-brain axis.
참고문헌 (36)
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