title: Characterization of duodenal expression and localization of fatty acid-sensing receptors in humans: relationships with body mass index.
abstract: Fatty acids (FAs) stimulate the secretion of gastrointestinal hormones, including cholecystokinin (CCK) and glucagon like peptide-1 (GLP-1), which suppress energy intake. In obesity, gastrointestinal responses to FAs are attenuated. Recent studies have identified a key role for the FA-sensing receptors cluster of differentiation (CD)36, G protein-coupled receptor (GPR)40, GPR120, and GPR119 in mediating gastrointestinal hormone secretion. This study aimed to determine the expression and localization of these receptors in the duodenum of humans and to examine relationships with obesity. Duodenal mucosal biopsies were collected from nine lean [body mass index (BMI): 22 ± 1 kg/m2], six overweight (BMI: 28 ± 1 kg/m2), and seven obese (BMI: 49 ± 5 kg/m2) participants. Absolute levels of receptor transcripts were quantified using RT-PCR, while immunohistochemistry was used for localization. Transcripts were expressed in the duodenum of lean, overweight, and obese individuals with abundance of CD36>>GPR40>GPR120>GPR119. Expression levels of GPR120 (r = 0.46, P = 0.03) and CD36 (r = 0.69, P = 0.0004) were directly correlated with BMI. There was an inverse correlation between expression of GPR119 with BMI (r2 = 0.26, P = 0.016). Immunolabeling studies localized CD36 to the brush border membrane of the duodenal mucosa and GPR40, GPR120, and GPR119 to enteroendocrine cells. The number of cells immunolabeled with CCK (r = -0.54, P = 0.03) and GLP-1 (r = -0.49, P = 0.045) was inversely correlated with BMI, such that duodenal CCK and GLP-1 cell density decreased with increasing BMI. In conclusion, CD36, GPR40, GPR120, and GPR119 are expressed in the human duodenum. Transcript levels of duodenal FA receptors and enteroendocrine cell density are altered with increasing BMI, suggesting that these changes may underlie decreased gastrointestinal hormone responses to fat and impaired energy intake regulation in obesity.
authors.affiliation: University of Adelaide Discipline of Medicine, Adelaide, South Australia, Australia; National Health and Medical Research Council Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, South Australia, Australia; and tanya.little@adelaide.edu.au.
authors.forename: Tanya J
authors.initials: TJ
authors.lastname: Little
authors.affiliation: University of Adelaide Discipline of Medicine, Adelaide, South Australia, Australia;
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Isaacs
authors.affiliation: University of Adelaide Discipline of Medicine, Adelaide, South Australia, Australia; National Health and Medical Research Council Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, South Australia, Australia; and.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Young
authors.affiliation: University of Adelaide Discipline of Medicine, Adelaide, South Australia, Australia;
authors.forename: Raffael
authors.initials: R
authors.lastname: Ott
authors.affiliation: National Health and Medical Research Council Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, South Australia, Australia; and Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors.forename: Nam Q
authors.initials: NQ
authors.lastname: Nguyen
authors.affiliation: University of Adelaide Discipline of Medicine, Adelaide, South Australia, Australia; National Health and Medical Research Council Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, South Australia, Australia; and Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Rayner
authors.affiliation: University of Adelaide Discipline of Medicine, Adelaide, South Australia, Australia; National Health and Medical Research Council Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, South Australia, Australia; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Horowitz
authors.affiliation: University of Adelaide Discipline of Medicine, Adelaide, South Australia, Australia; National Health and Medical Research Council Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, South Australia, Australia; and.
authors.forename: Christine
authors.initials: C
authors.lastname: Feinle-Bisset
mesh_terms: D000328:Adult; D001706:Biopsy; D015992:Body Mass Index; D018955:CD36 Antigens / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D004386:Duodenum / Q000737:chemistry* / Q000378:metabolism; D002149:Energy Intake; D019858:Enteroendocrine Cells / Q000737:chemistry / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005247:Feeding Behavior; D005260:Female; D006184:Habits; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D050177:Overweight / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018955:CD36 Antigens; C473034:FFAR1 protein, human; C519853:FFAR4 protein, human; D005227:Fatty Acids; C519854:GPR119 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled
keywords: CD36; GPR119; GPR120; GPR40; free fatty acid; nutrient sensing; receptor; small intestine