title: 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.affiliation: Department of Medicine, Duke University, Durham, North Carolina 27710, USA.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Chandra
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Rafiq A
authors.initials: RA
authors.lastname: Shahid
authors.forename: Steven R
authors.initials: SR
authors.lastname: Vigna
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Freedman
authors.forename: Rodger A
authors.initials: RA
authors.lastname: Liddle
mesh_terms: D000818:Animals; D016466:CHO Cells; D020013:Calcium Signaling; D002766:Cholecystokinin / Q000097:blood / Q000378:metabolism*; D006224:Cricetinae; D019858:Enteroendocrine Cells / Q000378:metabolism; D005227:Fatty Acids / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism; D008074:Lipoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*
chemical_list: D005227:Fatty Acids; C583885:Ildr1 protein, mouse; D008074:Lipoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D002766:Cholecystokinin