Characterization of duodenal expression and localization of fatty acid-sensing receptors in humans: Relationships with body mass index

Tanya J. Little, Nicole Isaacs, Richard Young, Raffael Ott, Nam Q. Nguyen, Christopher K. Rayner, Michael Horowitz, Christine Feinle-Bisset

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

LanguageEnglish
PagesG958-G967
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume307
Issue number10
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • CD36
  • Free fatty acid
  • GPR119
  • GPR120
  • GPR40
  • Nutrient sensing
  • Receptor
  • Small intestine

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Little, Tanya J. ; Isaacs, Nicole ; Young, Richard ; Ott, Raffael ; Nguyen, Nam Q. ; Rayner, Christopher K. ; Horowitz, Michael ; Feinle-Bisset, Christine. / Characterization of duodenal expression and localization of fatty acid-sensing receptors in humans : Relationships with body mass index. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2014 ; Vol. 307, No. 10. pp. G958-G967.
@article{eadd98be95a743ffa8edf006a668cfd0,
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.",
keywords = "CD36, Free fatty acid, GPR119, GPR120, GPR40, Nutrient sensing, Receptor, Small intestine",
author = "Little, {Tanya J.} and Nicole Isaacs and Richard Young and Raffael Ott and Nguyen, {Nam Q.} and Rayner, {Christopher K.} and Michael Horowitz and Christine Feinle-Bisset",
year = "2014",
month = "1",
day = "1",
doi = "10.1152/ajpgi.00134.2014",
language = "English",
volume = "307",
pages = "G958--G967",
journal = "American Journal of Physiology - Gastrointestinal and Liver Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "10",

}

Characterization of duodenal expression and localization of fatty acid-sensing receptors in humans : Relationships with body mass index. / Little, Tanya J.; Isaacs, Nicole; Young, Richard; Ott, Raffael; Nguyen, Nam Q.; Rayner, Christopher K.; Horowitz, Michael; Feinle-Bisset, Christine.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 307, No. 10, 01.01.2014, p. G958-G967.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Characterization of duodenal expression and localization of fatty acid-sensing receptors in humans

T2 - American Journal of Physiology - Gastrointestinal and Liver Physiology

AU - Little, Tanya J.

AU - Isaacs, Nicole

AU - Young, Richard

AU - Ott, Raffael

AU - Nguyen, Nam Q.

AU - Rayner, Christopher K.

AU - Horowitz, Michael

AU - Feinle-Bisset, Christine

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

KW - CD36

KW - Free fatty acid

KW - GPR119

KW - GPR120

KW - GPR40

KW - Nutrient sensing

KW - Receptor

KW - Small intestine

UR - http://www.scopus.com/inward/record.url?scp=84922392813&partnerID=8YFLogxK

U2 - 10.1152/ajpgi.00134.2014

DO - 10.1152/ajpgi.00134.2014

M3 - Article

VL - 307

SP - G958-G967

JO - American Journal of Physiology - Gastrointestinal and Liver Physiology

JF - American Journal of Physiology - Gastrointestinal and Liver Physiology

SN - 0193-1857

IS - 10

ER -