Stomach clusterin as a gut-derived feeding regulator

Area of Science:

• Endocrinology
• Neuroscience
• Gastroenterology

Background:

• The stomach is recognized as a key endocrine organ regulating feeding behavior.
• Gut-derived hormones like ghrelin and cholecystokinin influence feeding via the vagus nerve.
• The peripheral function of clusterin in feeding regulation was previously uncharacterized.

Discussion:

• Clusterin administration suppressed fasting-induced food intake in mice.
• Its effects on feeding were modulated by interactions with cholecystokinin and ghrelin.
• Vagotomy abolished clusterin-induced feeding suppression, highlighting the vagus nerve's role.

Key Insights:

• The stomach expresses high levels of clusterin, particularly in enteroendocrine cells.
• Gastric clusterin levels decrease with fasting and recover upon refeeding.
• Stomach-specific clusterin overexpression reduces food intake, confirming its peripheral role.

Outlook:

• Gastric clusterin acts as a gut-derived peptide regulating feeding via the gut-brain axis.
• Further research can explore clusterin's therapeutic potential in appetite control.
• Understanding clusterin's signaling pathways may reveal new targets for metabolic disorder treatments.