Abstract

BackgroundStomach is an integral part of the energy balance regulating circuit. Studies exploring the effects of cross-system changes in the energy homeostasis in stomach tissue are scarce. The proximity of the stomach to liver - the most common secondary target affected by obesity – suggests that these two organs are exposed to each other’s local secretion. Therefore, we aimed at expression profiling of energy metabolism associated genes in the gastric tissue of obese non-alcoholic fatty liver disease (NAFLD) patients.MethodsA total of 24 patients with histologically-proven NAFLD were included. In the gastric tissue, gene expression profiling of 84 energy metabolism associated genes was carried out.ResultsThe accumulation of the fat in the liver parenchyma is accompanied by downregulation of genes encoding for carboxypeptidase E (CPE) and Interleukin 1B (IL1B) in the gastric mucosa of same patient. In patients with high grade hepatic steatosis, Interleukin 1 beta encoding gene with anorexigenic function, IL1B was downregulated. The levels expression of 21 genes, including ADRA2B, CNR1 and LEP were significantly altered in the gastric tissue of NAFLD patients with hepatic inflammation. There were also indications of an increase in the opioid signaling within gastric mucosa that may results in a shift to proinflammatory environment within this organ and contribute to systemic inflammation and the pathogenic processes in hepatic parenchyma.ConclusionsWe have shown differential expression of energy metabolism associated genes in the gastric tissue of obese NAFLD patients. Importantly, these gene expression profiles are associated with changes in the hepatic parenchyma as reflected in increased scores for hepatic steatosis, inflammation, fibrosis and NASH. This study suggests the complex interplay of multiple organs in the pathogenesis of obesity-related complications such as NAFLD and provides further evidence supporting an important role for gastric tissue in promoting obesity-related complications.

Highlights

  • Stomach is an integral part of the energy balance regulating circuit

  • One of the best examples of the endocrine role of the stomach is seen in its production of the ghrelin, obestatin and leptin, hormones that are known to contribute to many chronic diseases asscociated with obesity [5,6,7]

  • We further explore this relationship by gene expression profiling of energy metabolism associated genes in the gastric tissue of obese non-alcoholic fatty liver disease (NAFLD) patients

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Summary

Introduction

Stomach is an integral part of the energy balance regulating circuit. Studies exploring the effects of cross-system changes in the energy homeostasis in stomach tissue are scarce. Energy balance is regulated by a milieu of hormones, cytokines and neurotransmitters. This homeostatic regulation integrates signals from the central nervous system and various peripheral organs and ensures that despite fluctuations in daily food and energy intake, the variation in day to day weight, in most cases, remains. Several recent studies have suggested a role of these molecules in systemic inflammation [8,9,10]. This indicates the necessity of further studies on the role of gastric tissue in obesity and obesity-related disorders

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