Real-time PCR based gene expression profiling in the tissues collected form bariatric surgery patients
Rohini Mehta, A. Birerdinc. A. Baranova
This is a collaborative project between
Molecular and Microbiology Department, College of Science,George Mason University, Fairfax, VA
Translational Reseach Institute, Inova Hospital, VA
Morbid obesity and the chronic diseases associated with metabolic syndrome have, in recent years, taken the lead in national public health concerns. Morbid obesity has been linked to a variety of severe, progressively degenerating conditions such as NASH, NAFLD, reproductive and cardiovascular disorders (Baranova et al. 2007). The increasing toll on individuals and public health resources alike has spurred the scientific community to investigate the causes and consequences of this emerging disease. Increasingly, research from various institutions and study centers is showing that morbid obesity is a chronic inflammatory condition seemingly due to inflammatory cytokines produced in adipose tissue (Csendes et al 2008).
A growing number of these cytokines have been profiled and rudimentary pathways have been established. Recent studies using adipocytes and preadipocytes have determined that these cells indeed produce cytokines such as IL-6, IL-10, or TNF-a, chemokines including MCP-1 (CLL2) and IL-8 (CXCL-8), and adipokines such as leptin, resistin, visfatin and adiponectin. In fact white adipose tissue (WAT) has been found to be involved in the regulation of metabolism and inflammation, via control of energy homeostasis with the production of cytokines such as Leptin, IL-6, and IL-1/IL-Ra (Juge-Aubry et al 2005).
Leptin for example, has been extensively studied and found to have, in addition to its membrane bound functions, a neuroendrocrine effect in the control of food intake and energy expenditure. In addition, Leptin has been shown to bind to various types of organs, including the intestines, liver, kidney, skin, stomach, heart, spleen, and lung indicating that this hormone may have a large span of affects including ectopic lipid deposition, influencing insulin sensitivity in muscle and liver tissues, and providing an interaction point between the endocrine and immune systems. (De Luis et al. 2009).
Cytokines and adipokines are produced in adipose tissue and secreted in circulation. Through the blood vessels, they travel to other organs and tissue and initiate a number of signaling cascades contributing to systemic inflammatory background associated with overweight and obesity. As obesity is often associated with gastritis, it is plausible that gastric tissue is one of the target organs of adipocytokines.
To date, very little is known about what receptors for inflammatory cytokines are present in the gastric tissue. It is possible that cytokine receptor profile in the gastric tissue reflects some some aspects of obesity, for example, its association with metabolic syndrome and the changes in the production of recently discovered stomach hormone, ghrelin. It is also not know whether genes previously implicated to obesity in studies of the visceral adipose are also expressed in the gastric tissue and change their expression accordingly.
We plan to investigate the levels of mRNAs encoding inflammatory cytokine receptors in the three anatomically distinct portions of the stomach, with the ultimate goal of correlating gene expression profiles in the gastric tissue with adipocytokine profiles in the serum of morbidly obese patients.
- 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 Aug;17(8):1111-8. PubMed PMID: 17953248.
- Batra A, Zeitz M, Siegmund B. Adipokine signaling in inflammatory bowel disease. Inflamm Bowel Dis. 2009 Apr 30. [Epub ahead of print] PubMed PMID: 19408337.
- Csendes A, Burgos AM, Roizblatt D, Garay C, Bezama P. Inflammatory Response Measured By Body Temperature, C-Reactive Protein and White Blood Cell Count 1, 3, and 5 Days After Laparotomic or Laparoscopic Gastric Bypass Surgery. Obes Surg. 2008 Oct 2. [Epub ahead of print] PubMed PMID: 18830782.
- De Luis DA, Perez Castrillon JL, Duenas A. Leptin and obesity. Minerva Med. 2009 Jan 30. [Epub ahead of print] PubMed PMID: 19182739.
De Smet B, Mitselos A, Depoortere I. Motilin and ghrelin as prokinetic drug targets. Pharmacol Ther. 2009 May 6. [Epub ahead of print] PubMed PMID: 19427331.
- Juge-Aubry CE, Henrichot E, Meier CA. Adipose tissue: a regulator of inflammation. Best Pract Res Clin Endocrinol Metab. 2005 Dec;19(4):547-66. Review. PubMed PMID: 16311216.
- Milke García Mdel P. [Ghrelin: beyond hunger regulation]. Rev Gastroenterol Mex. 2005 Oct-Dec;70(4):465-74. Review. Spanish. PubMed PMID: 17058987.
- Okamatsu Y, Matsuda K, Hiramoto I, Tani H, Kimura K, Yada Y, Kakuma T, Higuchi S, Kojima M, Matsuishi T. Ghrelin and leptin modulate immunity and liver function in overweight children. Pediatr Int. 2009 Feb;51(1):9-13. PubMed PMID: 19371271.