Apolipoprotein A-IV enhances cholecystokinnin secretion

Area of Science:

• Gastroenterology
• Metabolism
• Molecular Biology

Background:

• Cholecystokinin (CCK) and apolipoprotein A-IV (ApoA-IV) are key gastrointestinal peptides regulating energy homeostasis.
• Both peptides are secreted in response to dietary lipids and possess satiating properties.
• The precise interaction and regulatory mechanisms between ApoA-IV and CCK secretion remain incompletely understood.

Purpose of the Study:

• To investigate the regulatory role of apolipoprotein A-IV (ApoA-IV) in cholecystokinin (CCK) secretion.
• To elucidate the molecular mechanism by which ApoA-IV influences CCK gene expression and release.

Main Methods:

• Comparison of Cck gene expression in the duodenum of ApoA-IV knockout (ApoA-IV-KO) and wild-type (WT) mice under various feeding conditions.
• In vitro studies using STC-1 cells with lysophosphatidic acid receptor 5 (LPAR5) knockdown via siRNA.
• Assessment of CCK gene expression and protein release in response to ApoA-IV stimulation.

Main Results:

• Basal and lipid-stimulated Cck gene expression were significantly reduced in the duodenum of ApoA-IV-KO mice compared to WT mice.
• Recombinant ApoA-IV protein increased Cck gene expression and CCK release in STC-1 cells.
• The stimulatory effect of ApoA-IV on CCK was attenuated when LPAR5 expression was knocked down.

Conclusions:

• Dietary lipid-induced ApoA-IV is associated with Cck synthesis in the duodenum.
• ApoA-IV directly enhances CCK release through the activation of a LPAR5-dependent pathway.
• These findings reveal a novel molecular link between ApoA-IV and CCK in regulating appetite and energy balance.