Expression of Inflammation-Related Genes Is Altered in Gastric Tissue of Patients with Advanced Stages of NAFLD

Rohini Mehta,Zobair M Younossi,Arpan Neupane,Vikas Chandhoke,Arian Afendy,Hazem Elariny,Ancha Baranova,Amirhossein Shamsaddini,Aybike Birerdinc

doi:10.1155/2013/684237

Abstract

Obesity is associated with chronic low-grade inflammation perpetuated by visceral adipose. Other organs, particularly stomach and intestine, may also overproduce proinflammatory molecules. We examined the gene expression patterns in gastric tissue of morbidly obese patients with nonalcoholic fatty liver disease (NAFLD) and compared the changes in gene expression in different histological forms of NAFLD. Stomach tissue samples from 20 morbidly obese NAFLD patients who were undergoing sleeve gastrectomy were profiled using qPCR for 84 genes encoding inflammatory cytokines, chemokines, their receptors, and other components of inflammatory cascades. Interleukin 8 receptor-beta (IL8RB) gene overexpression in gastric tissue was correlated with the presence of hepatic steatosis, hepatic fibrosis, and histologic diagnosis of nonalcoholic steatohepatitis (NASH). Expression levels of soluble interleukin 1 receptor antagonist (IL1RN) were correlated with the presence of NASH and hepatic fibrosis. mRNA levels of interleukin 8 (IL8), chemokine (C-C motif) ligand 4 (CCL4), and its receptor chemokine (C-C motif) receptor type 5 (CCR5) showed a significant increase in patients with advanced hepatic inflammation and were correlated with the severity of the hepatic inflammation. The results of our study suggest that changes in expression patterns for inflammatory molecule encoding genes within gastric tissue may contribute to the pathogenesis of obesity-related NAFLD.

Highlights

Obesity is a multisystem disorder characterized by an excessive increase in the adipose tissue
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of diseases ranging from relatively benign fatty liver to nonalcoholic steatohepatitis, or NASH, characterized by inflammation and ballooning degeneration of hepatocytes, which may progress to fibrosis or cirrhosis
A number of pathways, such as enhanced oxidative stress, increased susceptibility to apoptosis, and insulin resistance have been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) [11], little is known about the triggers of the progression

Summary

Introduction

Obesity is a multisystem disorder characterized by an excessive increase in the adipose tissue. The regulation of the size of fat stores is a complex process and involves both central and peripheral tissues [1, 3] and over 50 secreted molecules, such as the adipocytic hormones leptin and adiponectin [4, 5], gastric ghrelin [6, 7], and intestinal cholecystokinin [8]. Many of these molecules play a role in various diseases associated with obesity, nonalcoholic fatty liver disease (NAFLD) [7, 9]. A number of pathways, such as enhanced oxidative stress, increased susceptibility to apoptosis, and insulin resistance have been implicated in the pathogenesis of NAFLD [11], little is known about the triggers of the progression

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