Apolipoprotein A-IV is involved in detection of lipid in the rat intestine - PubMed (original) (raw)
Apolipoprotein A-IV is involved in detection of lipid in the rat intestine
K L Whited et al. J Physiol. 2005.
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.
Figures
Figure 1. Lipid-induced inhibition of gastric emptying is significantly attenuated in apo A-IV knockout mice
Gastric emptying, expressed as half emptying time, of test meals differing in fat content was measured in freely fed apo A-IV wildtype and knockout mice using nuclear scintigraphy. In wildtype mice, the rate of gastric emptying was significantly inhibited by an increase in the fat content of the ingested test meals. In apo A-IV−/− mice, the inhibitory effect of lipid on gastric emptying was significantly attenuated (*P < 0.0001 and **P < 0.01, wildtype versus knockout, n = 9 apo A-IV+/+ and n = 13 apo A-IV−/−). Error bars are
s.e.m.
Figure 2. Lipid-induced inhibition of gastric acid secretion is abolished in apo A-IV knockout mice
A, time course changes in gastric acid secretion in individual apo A-IV wildtype and knockout mice. Gastric acid secretion in anaesthetized mice was continuously measured by back titration in response to intragastric perfusion with peptone (_t_0-_t_150) and duodenal perfusion with Intralipid (_t_90-_t_150). In both the wildtype mouse and knockout mouse, intragastric peptone stimulated gastric acid secretion, but duodenal lipid infusion inhibited meal-stimulated gastric acid secretion only in the wildtype control. B, intestinal lipid inhibition of gastric acid secretion in apo A-IV knockout (n = 5) and wildtype controls (n = 5) during basal, intragastric peptone and intragastric peptone, together with intestinal lipid perfusion. In apo A-IV−/− mice, basal and peptone-stimulated gastric acid secretion were significantly higher compared to apo A-IV+/+ mice (basal; *P < 0.0001, peptone stimulated; **P < 0.01). In both wildtype and apo A-IV knockout mice, intragastric peptone significantly stimulated gastric acid secretion, but duodenal lipid infusion inhibited meal-stimulated gastric acid secretion only in the wildtype control (*P < 0.0001). Error bars are
s.e.m.
Figure 3. Lipid-induced Fos protein expression in the nucleus of the solitary tract (NTS) is attenuated in apo A-IV knockout mice
A, cytoarchitecture map for photomicrographs of mice brainstem. NTS = nucleus of the solitary tract; CC = central canal; AP = area postrema; DMN = dorsal motor nucleus of vagus; HN = hypoglossal nucleus. B, photomicrographs of mouse brainstem showing activation of Fos expression in neurones in the nucleus of the solitary tract at the area postrema in apo A-IV wildtype control and knockout mice following saline or Intralipid gavage. a, apo A-IV+/+ saline; b, apo A-IV−/− saline; c, apo A-IV+/+ Intralipid d, apo A-IV−/− Intralipid.
Figure 4. Lipid-induced Fos protein expression in the nucleus of the solitary tract (NTS) is attenuated in apo A-IV knockout mice
Activation of Fos expression at different levels of the NTS in apo A-IV knockout and wildtype control mice with saline (n = 4), saline and devazepide
i.p.
(n = 4), Intralipid gavage (n = 4) or Intralipid gavage and devazepide
i.p.
(n = 4). A, pre-area postrema (*P < 0.05); B, at-area postrema (*P < 0.001, note a change in axis scale for this graph); C, post-area postrema (*P < 0.001, **P < 0.01). Error bars are
s.e.m.
Figure 5. No gross difference in expression of duodenal CCK endocrine cells in apo A-IV wildtype and knockout mice
Photomicrographs of mice duodenum showing distribution of CCK-expressing endocrine cells in a chow-fed apo A-IV wildtype control and knockout mouse. A, apo A-IV+/+ transverse section; B, apo A-IV−/− transverse section; C, apo A-IV+/+ longitudinal section; D, apo A-IV−/− longitudinal section. Scale bar = 100 μs.
References
- Apfelbaum TF, Davidson NO, Glickman RM. Apolipoprotein A-IV synthesis in rat intestine: regulation by dietary triglyceride. Am J Physiol. 1987;252:G662–G666. -PubMed
- Baroukh N, Ostos MA, Vergnes L, Recalde D, Staels B, Fruchart J, Ochoa A, Castro G, Zakin MM. Expression of human apolipoprotein A-I/C-III/A-IV gene cluster in mice reduces atherogenesis in response to a high fat-high cholesterol diet. FEBS Lett. 2001;502:16–20. -PubMed
- Berthoud HR, Kressel M, Raybould HE, Neuhuber WL. Vagal sensors in the rat duodenal mucosa: distribution and structure as revealed by in vivo DiI-tracing. Anat Embryol. 1995;191:203–212. -PubMed
- Berthoud HR, Neuhuber WL. Functional and chemical anatomy of the afferent vagal system. Auton Neurosci. 2000;85:1–17. -PubMed
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