Please use this identifier to cite or link to this item:
|Scopus||Web of Science®||Altmetric|
|Title:||Characterization of duodenal expression and localization of fatty acid-sensing receptors in humans: relationships with body mass index|
|Citation:||American Journal of Physiology. Gastrointestinal and Liver Physiology, 2014; 307(10):G958-G967|
|Publisher:||American Physiological Society|
|Tanya J. Little, Nicole J. Isaacs, Richard L. Young, Raffael Ott, Nam Q. Nguyen, Christopher K. Rayner, Michael Horowitz, and Christine Feinle-Bisset|
|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/m(2)], six overweight (BMI: 28 ± 1 kg/m(2)), and seven obese (BMI: 49 ± 5 kg/m(2)) 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 (r(2) = 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.|
|Keywords:||CD36; GPR119; GPR120; GPR40; free fatty acid; nutrient sensing; receptor; small intestine|
|Rights:||Copyright © 2014 the American Physiological Society|
|Appears in Collections:||Medicine publications|
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.