The online version of this article (doi:10.1186/1471-230X-14-72) contains supplementary material, which is available to authorized users.
Rohini Mehta, Aybike Birerdinc, Ancha Baranova contributed equally to this work.
The authors declare that they have no competing interests.
RM performed qPCRs and produced figures; ABir, ABar and RM wrote the manuscript; LW and RM performed statistical analysis; ZaY collected samples and performed chart reviews; AM and HE are bariatric surgeons who collected samples according to excusion and inclusion criteria; ZG reviewed and scored histological slides of the liver; ABar, ABir, VC and ZoY designed experiments and edited the manuscript. All authors read and approved the final manuscript.
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. 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.
A 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.
The 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.
We 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.
Estep M, Abawi M, Jarrar M, Wang L, Stepanova M, Elariny H, Moazez A, Goodman Z, Chandhoke V, Baranova A, Younossi ZM: Association of obestatin, ghrelin, and inflammatory cytokines in obese patients with non-alcoholic fatty liver disease. Obes Surg. 2011, 21: 1750-1757. 10.1007/s11695-011-0475-1. CrossRefPubMed
Wijngaarden MA, van der Zon GC, van Dijk KW, Pijl H, Guigas B: Effects of prolonged fasting on AMPK signaling, gene expression, and mitochondrial respiratory chain content in skeletal muscle from lean and obese individuals. J Cell Biol. 2013, 304: E1012-E1021.
Baranova A, Schlauch K, Elariny H, Jarrar M, Bennett C, Nugent C, Gowder SJ, Younoszai Z, Collantes R, Chandhoke V, Younossi ZM: Gene expression patterns in hepatic tissue and visceral adipose tissue of patients with non-alcoholic fatty liver disease. Obes Surg. 2007, 17: 1111-1118. 10.1007/s11695-007-9187-y. CrossRefPubMed
Yamaoka M, Maeda N, Nakamura S, Kashine S, Nakagawa Y, Hiuge-Shimizu A, Okita K, Imagawa A, Matsuzawa Y, Matsubara K, Funahashi T, Shimomura I: A pilot investigation of visceral fat adiposity and gene expression profile in peripheral blood cells. PLoS One. 2012, 7: e47377-10.1371/journal.pone.0047377. CrossRefPubMedPubMedCentral
Vrabie CD, Cojocaru M, Waller M, Sindelaru R, Copaescu C: The main histopathological gastric lesions in obese patients who underwent sleeve gastrectomy. Dicle Med J. 2010, 37: 97-103.
Gündoğan M, Çalli Demırkan N, Tekın K, Aybek H: Gastric histopathological findings and ghrelin expression in morbid obesity. Turk Patoloji Derg. 2013, 29: 19-26. PubMed
Ryysy L, Häkkinen AM, Goto T, Vehkavaara S, Westerbacka J, Halavaara J, Yki-Järvinen H: Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients. Diabetes. 2000, 49: 749-758. 10.2337/diabetes.49.5.749. CrossRefPubMed
Seppälä-Lindroos A, Vehkavaara S, Häkkinen AM, Goto T, Westerbacka J, Sovijärvi A, Halavaara J, Yki-Järvinen H: Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab. 2002, 87: 3023-3028. 10.1210/jcem.87.7.8638. CrossRefPubMed
Charlton M, Viker K, Krishnan A, Sanderson S, Veldt B, Kaalsbeek AJ, Kendrick M, Thompson G, Que F, Swain J, Sarr M: Differential expression of lumican and fatty acid binding protein-1: new insights into the histologic spectrum of nonalcoholic fatty liver disease. Hepatology. 2009, 49: 1375-1384. 10.1002/hep.22927. CrossRefPubMedPubMedCentral
Roden M: Muscle triglycerides and mitochondrial function: possible mechanisms for the development of type 2 diabetes. Int J Obes (Lond). 2005, 29: S111-S115. CrossRef
Varma V, Yao-Borengasser A, Rasouli N, Bodles AM, Phanavanh B, Lee MJ, Starks T, Kern LM, Spencer HJ, McGehee RE, Fried SK, Kern PA: Human visfatin expression: relationship to insulin sensitivity, intramyocellular lipids, and inflammation. J Clin Endocrinol Metab. 2007, 92: 666-672. 10.1210/jc.2006-1303. CrossRefPubMed
Gutierrez-Grobe Y, Villalobos-Blasquez I, Sánchez-Lara K, Villa AR, Ponciano-Rodríguez G, Ramos MH, Chavez-Tapia NC, Uribe M, Méndez-Sánchez N: High ghrelin and obestatin levels and low risk of developing fatty liver. Ann Hepatol. 2010, 9: 52-57. PubMed
Reyes TM, Sawchenko PE: Involvement of the arcuate nucleus of the hypothalamus in interleukin-1-induced anorexia. J Neurosci. 2002, 22: 5091-5099. PubMed
Kornman KS: Interleukin 1 genetics, inflammatory mechanisms, and nutrigenetic opportunities to modulate diseases of aging. Am J Clin Nutr. 2006, 83: 475S-483S. PubMed
De Datta D, Bhattacharjya S, Maitra M, Datta A, Choudhury A, Dhali GK, Roychoudhury S: IL1B induced Smad 7 negatively regulates gastrin expression. PLoS One. 2011, 6: e14775-10.1371/journal.pone.0014775. CrossRef
Nov O, Shapiro H, Ovadia H, Tarnovscki T, Dvir I, Shemesh E, Kovsan J, Shelef I, Carmi Y, Voronov E, Apte RN, Lewis E, Haim Y, Konrad D, Bashan N, Rudich A: Interleukin-1β regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability. PLoS One. 2013, 8: e53626-10.1371/journal.pone.0053626. CrossRefPubMedPubMedCentral
Egerod KL, Engelstoft MS, Grunddal KV, Nøhr MK, Secher A, Sakata I, Pedersen J, Windeløv JA, Füchtbauer EM, Olsen J, Sundler F, Christensen JP, Wierup N, Olsen JV, Holst JJ, Zigman JM, Poulsen SS, Schwartz TW: A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin. Endocrinology. 2012, 153: 5782-5795. 10.1210/en.2012-1595. CrossRefPubMed
Mazella J, Béraud-Dufour S, Devader C, Massa F, Coppola T: Neurotensin and its receptors in the control of glucose homeostasis. Front Endocrinol (Lausanne). 2012, 3: 143-
Zhao W, Fong O, Muise ES, Thompson JR, Weingarth D, Qian S, Fong TM: Genome-wide expression profiling revealed peripheral effects of cannabinoid receptor 1 inverse agonists in improving insulin sensitivity and metabolic parameters. Mol Pharmacol. 2010, 78: 350-359. 10.1124/mol.110.064980. CrossRefPubMed
Pagano C, Pilon C, Calcagno A, Urbanet R, Rossato M, Milan G, Bianchi K, Rizzuto R, Bernante P, Federspil G, Vettor R: The endogenous cannabinoid system stimulates glucose uptake in human fat cells via phosphatidylinositol 3-kinase and calcium-dependent mechanisms. J Clin Endocrinol Metab. 2007, 92: 4810-4819. 10.1210/jc.2007-0768. CrossRefPubMed
Tam J, Cinar R, Liu J, Godlewski G, Wesley D, Jourdan T, Szanda G, Mukhopadhyay B, Chedester L, Liow JS, Innis RB, Cheng K, Rice KC, Deschamps JR, Chorvat RJ, McElroy JF, Kunos G: Peripheral cannabinoid-1 receptor inverse agonism reduces obesity by reversing leptin resistance. Cell Metab. 2012, 16: 167-179. 10.1016/j.cmet.2012.07.002. CrossRefPubMed
Aller R, de Luis DA, Pacheco D, Velasco MC, Conde R, Izaola O, González Sagrado M: Influence of G1359A polimorphysm of the cannabinoid receptor gene (CNR1) on insulin resistance and adipokines in patients with non alcoholic fatty liver disease. Nutr Hosp. 2012, 27: 1637-1642. PubMed
- Expression of energy metabolism related genes in the gastric tissue of obese individuals with non-alcoholic fatty liver disease
Zobair M Younossi
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II