Immunoglobulin-like domain containing receptor 1 mediates fat-stimulated cholecystokinin secretion
Rashmi Chandra, … , Neil J. Freedman, Rodger A. Liddle
Rashmi Chandra, … , Neil J. Freedman, Rodger A. Liddle
Published July 25, 2013
Citation Information: J Clin Invest. 2013;123(8):3343-3352. https://doi.org/10.1172/JCI68587.
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Research Article Gastroenterology

Immunoglobulin-like domain containing receptor 1 mediates fat-stimulated cholecystokinin secretion

Abstract

Cholecystokinin (CCK) is a satiety hormone produced by discrete enteroendocrine cells scattered among absorptive cells of the small intestine. CCK is released into blood following a meal; however, the mechanisms inducing hormone secretion are largely unknown. Ingested fat is the major stimulant of CCK secretion. We recently identified a novel member of the lipoprotein remnant receptor family known as immunoglobulin-like domain containing receptor 1 (ILDR1) in intestinal CCK cells and postulated that this receptor conveyed the signal for fat-stimulated CCK secretion. In the intestine, ILDR1 is expressed exclusively in CCK cells. Orogastric administration of fatty acids elevated blood levels of CCK in wild-type mice but not Ildr1-deficient mice, although the CCK secretory response to trypsin inhibitor was retained. The uptake of fluorescently labeled lipoproteins in ILDR1-transfected CHO cells and release of CCK from isolated intestinal cells required a unique combination of fatty acid plus HDL. CCK secretion secondary to ILDR1 activation was associated with increased [Ca2+]i, consistent with regulated hormone release. These findings demonstrate that ILDR1 regulates CCK release through a mechanism dependent on fatty acids and lipoproteins and that absorbed fatty acids regulate gastrointestinal hormone secretion.

Authors

Rashmi Chandra, Yu Wang, Rafiq A. Shahid, Steven R. Vigna, Neil J. Freedman, Rodger A. Liddle

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Figure 6

Effects of fatty acids and lipoproteins on intracellular calcium fluorescence in CCK cells.

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Effects of fatty acids and lipoproteins on intracellular calcium fluores...
CCK-EGFP cells were isolated from the intestines of wild-type CCK-EGFP and Ildr1–/– CCK-EGFP mice and enriched by FACS. Cells were loaded with calcium-sensitive dye (X-rhod-1) and incubated first with lipoproteins (100 μg protein/ml) or C12 (100 μM), followed by lipoprotein plus C12, and finally with KCl (50 mM). (A) The responses of representative wild-type CCK-EGFP or Ildr1–/– CCK-EGFP cells to lipoproteins and lipoprotein plus C12 are shown. Change in fluorescence from green to yellow to red indicates elevation in [Ca2+]i. An increase in [Ca2+]i with KCl was used to confirm the viability of cells at the conclusion of each experiment. Results are representative of at least 3 experiments. (B) Change in fluorescence intensity in wild-type CCK-EGFP and Ildr1–/– CCK-EGFP cells to C12 alone, HDL alone, HDL plus C12, and KCl. (C) Percentage of wild-type CCK-EGFP and Ildr1–/– CCK-EGFP cells that showed at least a 10% increase in Ca2+ fluorescence in response to HDL or HDL plus C12. The percentage of cells responding to C12 alone is represented by the dashed line. Scale bar: 5 μm.