Distribution of transient receptor potential vanilloid-1 channels in gastrointestinal tract of patients with morbid obesity

Abstract

Background: Transient receptor potential vanilloid-1 (TRPV1), a nonselective cation channel, is activated by capsaicin, a pungent ingredient of hot pepper. Previous studies have suggested a link between obesity and capsaicin-associated pathways, and activation of TRPV1 may provide an alternative approach for obesity treatment. However, data on the TRPV1 distribution in human gastric mucosa are limited, and the degree of TRPV1 distribution in the gastric and duodenal mucosal cells of obese people in comparison with normal-weight individuals is unknown.

Aim: To clarify gastric and duodenal mucosal expression of TRPV1 in humans and compare TRPV1 expression in obese and healthy individuals.

Methods: Forty-six patients with a body mass index (BMI) of > 40 kg/m² and 20 patients with a BMI between 18-25 kg/m² were included. Simultaneous biopsies from the fundus, antrum, and duodenum tissues were obtained from subjects between the ages of 18 and 65 who underwent esophagogastroduodenoscopy. Age, sex, history of alcohol and cigarette consumption, and past medical history regarding chronic diseases and medications were accessed from patient charts and were analyzed accordingly. Evaluation with anti-TRPV1 antibody was performed separately according to cell types in the fundus, antrum, and duodenum tissues using an immunoreactivity score. Data were analyzed using SPSS 17.0.

Results: TRPV1 expression was higher in the stomach than in the duodenum and was predominantly found in parietal and chief cells of the fundus and mucous and foveolar cells of the antrum. Unlike foveolar cells in the antrum, TRPV1 was relatively low in foveolar cells in the fundus (4.92 ± 0.49 vs 0.48 ± 0.16, P < 0.01, Mann-Whitney U test). Additionally, the mucous cells in the duodenum also had low levels of TRPV1 compared to mucous cells in the antrum (1.33 ± 0.31 vs 2.95 ± 0.46, P < 0.01, Mann-Whitney U test). TRPV1 expression levels of different cell types in the fundus, antrum, and duodenum tissues of the morbidly obese group were similar to those of the control group. Staining with TRPV1 in fundus chief cells and antrum and duodenum mucous cells was higher in patients aged ≥ 45 years than in patients < 45 years (3.03 ± 0.42, 4.37 ± 0.76, 2.28 ± 0.55 vs 1.9 ± 0.46, 1.58 ± 0.44, 0.37 ± 0.18, P = 0.03, P < 0.01, P < 0.01, respectively, Mann-Whitney U test). The mean staining levels of TRPV1 in duodenal mucous cells in patients with diabetes and hypertension were higher than those in patients without diabetes and hypertension (diabetes: 2.11 ± 0.67 vs 1.02 ± 0.34, P = 0.04; hypertension: 2.42 ± 0.75 vs 1.02 ± 0.33, P < 0.01 Mann-Whitney U test).

Conclusion: The expression of TRPV1 is unchanged in the gastroduodenal mucosa of morbidly obese patients demonstrating that drugs targeting TRPV1 may be effective in these patients.

Keywords: Capsaicin; Immunohistochemistry; Morbid obesity; Obesity; Transient receptor potential channels; Transient receptor potential vanilloid 1; Transient receptor potential vanilloid cation channels.

Figure 1

Distribution of transient receptor potential vanilloid-1 channels in the gastroduodenal mucosa were demonstrated by immunohistochemical staining. A: Fundus; B: Antrum; C: Duodenum.

Figure 2

Comparison of immunoreactivity scores of foveolar cells in the fundus and antrum, mucous cells in the duodenum and antrum. A: Foveolar cells in the fundus and antrum; B: Mucous cells in the duodenum and antrum. IRS: Immunoreactivity score.

Figure 3

Duodenal mucous cells had higher immunoreactivity scores in patients with hypertension and diabetes. IRS: Immunoreactivity score; HT (+): Hypertensive; HT (-): Normotensive; DM (+): Diabetic; DM (-): Non-diabetic.