Apolipoprotein A‐IV is involved in detection of lipid in the rat intestine

Abstract

Long chain triglyceride (>C12) in the intestinal lumen potently inhibits gastric emptying and acid secretion via the vagal afferent pathway. While the mechanism of inhibition involves the formation of chylomicrons, the essential role of the apolipoprotein apo A-IV is unclear. Using apo A-IV -/-mice, we tested the hypothesis that inhibition of gastric emptying and gastric acid secretion in response to dietary lipid is dependent upon apo A-IV. As measured by nuclear scintigraphy in awake mice, gastric emptying of an ingested whole-egg meal was significantly faster in apo A-IV -/-knockout versus A-IV +/+ controls (34 ± 1 versus 54 ± 3 min, P < 0.0001). In anaesthetized A-IV +/+ mice, meal-stimulated gastric acid secretion was 59% inhibited by intestinal lipid infusion; this was abolished in apo A-IV -/-mice. Oral gavage of lipid in awake mice activated neurones throughout the nucleus of the solitary tract (NTS) in A-IV +/+ mice, measured by immunohistochemical localization of Fos protein expression. However, in the mid region of the NTS (bregma −7.32 to −7.76 mm), Fos expression in response to intestinal lipid was significantly decreased by 50% in apo A-IV -/-mice compared to A-IV +/+ controls. We conclude that activation of the vagal afferent pathway and inhibition of gastric function in response to dietary lipid is partly dependent upon apo A-IV.

Impact of murine intestinal apolipoprotein A-IV expression on regional lipid absorption, gene expression, and growth

“…Feeding studies revealed that, in the setting of a high dietary fat intake, apoA-IV facilitates weight gain and adipose tissue lipid storage, possibly by limiting the entry of dietary fatty acids into the distal gut, thereby attenuating secretion of gut hormones that suppress appetite and increase basal energy expenditure. Considering our observations in the light of past research on apoA-IV, we propose that by functioning as a nutrientresponsive modulator ( 15 ) of regional TG absorption and foregut motility ( 50,51 ), apoA-IV stands at the nexus of a complex neuroendocrine system that integrates feeding behavior, intestinal function, and energy utilization and storage. The function of apoA-IV in this system could help maintain positive energy balance during times of high lipid loads (e.g., in neonates) or impaired intestinal function (e.g., poststarvation [ 52 ]).…”

Apolipoprotein A-IV: a protein intimately involved in metabolism

“…In subsequent studies, purifi ed recombinant apoA-IV was found to signifi cantly inhibit gastric motility ( 89,90 ). apoA-IV KO mice have signifi cantly faster gastric emptying and greater secretion of gastric acid after an ingested meal ( 91 ). The action of apoA-IV to reduce gastric emptying is due to its being released from chylomicrons and initiating a negative feedback on gastric motility via the cholecystokinin-1 receptor (CCK-1R) on capsaicin-sensitive vagal afferent nerve terminals ( 91 ).…”

“…apoA-IV KO mice have signifi cantly faster gastric emptying and greater secretion of gastric acid after an ingested meal ( 91 ). The action of apoA-IV to reduce gastric emptying is due to its being released from chylomicrons and initiating a negative feedback on gastric motility via the cholecystokinin-1 receptor (CCK-1R) on capsaicin-sensitive vagal afferent nerve terminals ( 91 ). In addition to gastric emptying, centrally administered apoA-IV inhibits gastric acid secretion.…”

Methods for measurement of gastric motility

“…Similarly, the literature demonstrates the power of small animal scintigraphy to document biological effects in knockouts as well as pharmacological modulation (137,138).…”