Effect of Obesity on the Expression of Nutrient Receptors and Satiety Hormones in the Human Colon.

Lucas Baumard,Daniel Keszthelyi,Ad A M Masclee,Zsa Zsa R M Weerts,Madusha Peiris,Adina T Michael-Titus

doi:10.3390/nu13041271

Lucas Baumard, Daniel Keszthelyi + Show 4 more

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https://doi.org/10.3390/nu13041271

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Abstract

Background: Receptors located on enteroendocrine cells (EECs) of the colon can detect nutrients in the lumen. These receptors regulate appetite through a variety of mechanisms, including hormonal and neuronal signals. We assessed the effect of obesity on the expression of these G-protein coupled receptors (GPCRs) and hormones at both mRNA and protein level. Methods: qPCR and immunohistochemistry were used to examine colonic tissue from cohorts of patients from the Netherlands (proximal and sigmoid tissue) and the United Kingdom (tissue from across the colon) and patients were grouped by body mass index (BMI) value (BMI < 25 and BMI ≥ 25). Results: The mRNA expression of the hormones/signaling molecules serotonin, glucagon, peptide YY (PYY), CCK and somatostatin were not significantly different between BMI groups. GPR40 mRNA expression was significantly increased in sigmoid colon samples in the BMI ≥ 25 group, but not proximal colon. GPR41, GPR109a, GPR43, GPR120, GPRC6A, and CaSR mRNA expression were unaltered between low and high BMI. At the protein level, serotonin and PYY containing cell numbers were similar in high and low BMI groups. Enterochromaffin cells (EC) showed high degree of co-expression with amino acid sensing receptor, CaSR while co-expression with PYY containing L-cells was limited, regardless of BMI. Conclusions: While expression of medium/long chain fatty acid receptor GPR40 was increased in the sigmoid colon of the high BMI group, expression of other nutrient sensing GPCRs, and expression profiles of EECs involved in peripheral mechanisms of appetite regulation were unchanged. Collectively, these data suggest that in human colonic tissue, EEC and nutrient-sensing receptor expression profiles are not affected despite changes to BMI.

Highlights

Obesity is a significant and growing health issue facing the Western world [1,2].Obese adults are more susceptible to a wide range of comorbidities, including type 2 diabetes [3], metabolic disorders and abnormalities such as dyslipidaemia [4], cardiovascular disease [5]—including hypertension [6], stroke [7]—and a variety of cancers [8].Appetite is regulated to balance energy intake and expenditure by the release of hunger and satiety signals [9]
We have previously shown that agonist action at GPR41, GPR40, and GPR119 induces colonic EEC activation [49] and, importantly, that stimulation of GPR84 increases the release of glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and serotonin, demonstrating functional modulation of L and Enterochromaffin cells (EC) cells [45]
There was no significant change in the expression of tryptophan hydroxylase 1 (TPH1), glucagon, PYY or somatostatin, between the healthy body mass index (BMI) (

Summary

Introduction

Obesity is a significant and growing health issue facing the Western world [1,2].Obese adults are more susceptible to a wide range of comorbidities, including type 2 diabetes [3], metabolic disorders and abnormalities such as dyslipidaemia [4], cardiovascular disease [5]—including hypertension [6], stroke [7]—and a variety of cancers [8].Appetite is regulated to balance energy intake and expenditure by the release of hunger and satiety signals [9]. Appetite regulation can begin before food enters the body; the cephalic phase is initiated by sights and smells of food and by environmental effects such as time of day [10] Both mechanical and hormonal signals regulate food intake via central control from brain centres of appetite regulation, including the solitary tract nucleus in the brain stem [11,12]. The colon is the main source of peripheral serotonin [14] and holds the highest number and diversity of microbiota, with bacterial by-products such as short chain fatty acids (SCFA) playing a role in nutrient sensing and obesity Hormones such as PYY, CCK, and GLP-1 are released from the colon and can enter the circulation [15,16]. CCK can act on vagal fibres innervating the brain stem to alter gut motility, secretions from the pancreas and gall bladder activation [9]

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