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

R Chandra, Y Wang, RA Shahid… - The Journal of …, 2013 - Am Soc Clin Investig
R Chandra, Y Wang, RA Shahid, SR Vigna, NJ Freedman, RA Liddle
The Journal of clinical investigation, 2013Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation