Altered intestinal neuroendocrine gene expression in humans with obesity

Obesity (Silver Spring). 2015 Nov;23(11):2278-85. doi: 10.1002/oby.21253. Epub 2015 Sep 18.

Abstract

Objective: Gastrointestinal hormones are critically involved in the regulation of food intake and body weight. Previous studies support an interplay between gastrointestinal hormones and the serotonergic system. This study explored intestinal neuroendocrine expression patterns in humans with obesity versus nonobese humans.

Methods: Jejunum samples were collected from 164 humans with obesity (120 women; BMI (mean ± SD): 43.5 ± 6.6 kg/m(2) ) while they underwent Roux-en-Y gastric bypass surgery and from 18 nonobese humans (7 women; BMI: 23.5 ± 3.0 kg/m(2) ) undergoing distinct intestinal surgeries. mRNA expression of cholecystokinin (CCK), peptide YY3-36 (PYY), nesfatin1, ghrelin, ghrelin O-acyltransferase (GOAT), leptin, leptin receptor (leptinR), glucagon-like-peptide 1 receptor (GLP1R), serotonin transporter (SERT), tryptophan hydroxylase 1 (TPH1), and serotonin receptor 3A (5HT3A R) was determined with qRT-PCR. Ghrelin and GOAT protein expression was quantified using immunohistological stainings. Statistical analyses were performed with SPSS.

Results: Jejunum samples from humans with obesity showed a higher expression of GOAT (mRNA and protein), TPH1, and SERT mRNA compared with the nonobese humans (all P < 0.05). Positive correlations were observed between TPH1, CCK, PYY, and nesfatin1 in nonobese and GOAT, ghrelin, TPH1, SERT, CCK, and PYY in humans with obesity (all P < 0.01).

Conclusions: Our top-down approach substantiates the dysregulation of jejunal neuroendocrine hormones in obesity.

MeSH terms

  • Acyltransferases / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cholecystokinin / genetics
  • Female
  • Gastric Bypass
  • Gastrointestinal Hormones / genetics*
  • Gastrointestinal Hormones / metabolism
  • Gene Expression Regulation*
  • Ghrelin / genetics
  • Humans
  • Jejunum / metabolism*
  • Leptin / genetics
  • Middle Aged
  • Neuroendocrine Cells / metabolism*
  • Obesity, Morbid / genetics*
  • Obesity, Morbid / surgery
  • Peptide Fragments / genetics
  • Peptide YY / genetics
  • Weight Loss / physiology
  • Young Adult

Substances

  • Gastrointestinal Hormones
  • Ghrelin
  • Leptin
  • Peptide Fragments
  • Peptide YY
  • peptide YY (3-36)
  • Cholecystokinin
  • Acyltransferases
  • MBOAT4 protein, human