title: Expression of the Bitter Taste Receptor, T2R38, in Enteroendocrine Cells of the Colonic Mucosa of Overweight/Obese vs. Lean Subjects.
abstract: Bitter taste receptors (T2Rs) are expressed in the mammalian gastrointestinal mucosa. In the mouse colon, T2R138 is localized to enteroendocrine cells and is upregulated by long-term high fat diet that induces obesity. The aims of this study were to test whether T2R38 expression is altered in overweight/obese (OW/OB) compared to normal weight (NW) subjects and characterize the cell types expressing T2R38, the human counterpart of mouse T2R138, in human colon. Colonic mucosal biopsies were obtained during colonoscopy from 35 healthy subjects (20 OW/OB and 15 NW) and processed for quantitative RT-PCR and immunohistochemistry using antibodies to T2R38, chromogranin A (CgA), glucagon like peptide-1 (GLP-1), cholecystokinin (CCK), or peptide YY (PYY). T2R38 mRNA levels in the colonic mucosa of OW/OB were increased (> 2 fold) compared to NW subjects but did not reach statistical significance (P = 0.06). However, the number of T2R38 immunoreactive (IR) cells was significantly increased in OW/OB vs. NW subjects (P = 0.01) and was significantly correlated with BMI values (r = 0.7557; P = 0.001). In both OW/OB and NW individuals, all T2R38-IR cells contained CgA-IR supporting they are enteroendocrine. In both groups, T2R38-IR colocalized with CCK-, GLP1- or PYY-IR. The overall CgA-IR cell population was comparable in OW/OB and NW individuals. This study shows that T2R38 is expressed in distinct populations of enteroendocrine cells in the human colonic mucosa and supports T2R38 upregulation in OW/OB subjects. T2R38 might mediate host functional responses to increased energy balance and intraluminal changes occurring in obesity, which could involve peptide release from enteroendocrine cells.
authors: CURE/DDRC, Division of Digestive Diseases, Department Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors: Rocco
authors: R
authors: Latorre
authors: CURE/DDRC, Division of Digestive Diseases, Department Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.|Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors: Jennifer
authors: J
authors: Huynh
authors: Department of Veterinary Medical Science, University of Bologna, Bologna, Italy.
authors: Maurizio
authors: M
authors: Mazzoni
authors: Oppenheimer Family Center for Neurobiology of Stress, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors: Arpana
authors: A
authors: Gupta
authors: Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors: Elena
authors: E
authors: Bonora
authors: Department of Veterinary Medical Science, University of Bologna, Bologna, Italy.
authors: Paolo
authors: P
authors: Clavenzani
authors: CURE/DDRC, Division of Digestive Diseases, Department Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.|Oppenheimer Family Center for Neurobiology of Stress, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors: Lin
authors: L
authors: Chang
authors: CURE/DDRC, Division of Digestive Diseases, Department Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.|Oppenheimer Family Center for Neurobiology of Stress, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors: Emeran A
authors: EA
authors: Mayer
authors: Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors: Roberto
authors: R
authors: De Giorgio
authors: CURE/DDRC, Division of Digestive Diseases, Department Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.|Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors: Catia
authors: C
authors: Sternini
mesh_terms: D000328:Adult; D002766:Cholecystokinin / Q000032:analysis; D053379:Chromogranin A / Q000032:analysis; D003106:Colon / Q000737:chemistry / Q000166:cytology* / Q000473:pathology; D019858:Enteroendocrine Cells / Q000378:metabolism*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000032:analysis; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D050177:Overweight / Q000378:metabolism* / Q000473:pathology; D019894:Peptide YY / Q000032:analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D043562:Receptors, G-Protein-Coupled / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult; D000098706:Taste Receptors, Type 2
chemical_list: D053379:Chromogranin A; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin