Abstract
Background
Morbidly obese patients are at risk for nonalcoholic steatohepatitis (NASH) even in the absence of risk factors for liver disease. Unfortunately, NASH is usually not clinically evident, and a definitive, noninvasive test for NASH does not exist. Resistin, a cytokine originating from adipose tissue, is involved in insulin resistance and also initiates proinflammatory signaling from hepatic stellate cells. This study explores the relationship between resistin expression and liver pathology in bariatric surgery patients.
Methods
Blood samples from 30 patients undergoing bariatric surgery were collected. Total RNA was extracted and cDNA was synthesized. Quantitative RT-PCR was used to quantify relative gene expression using 18s rRNA gene as an internal control. Wedge liver biopsies from these patients were sectioned and stained. Based on a previously published scoring method, biopsies were assigned an overall NASH severity score and subscores for steatosis, inflammation, and fibrosis. Results were analyzed by using Student’s t test.
Results
Resistin mRNA levels ranged from 0.5 to 9.7. A group of five patients with very high resistin expression (>4) was identified. These patients had a significantly higher average NASH score compared with the rest of the group (7.9 vs. 4.48, p = 0.019). Steatosis and inflammation scores were significantly higher in the high-resistin group (p < 0.05 for both comparisons). There also was a trend toward higher fibrosis score in this group, which approached statistical significance (p = 0.051).
Conclusions
In morbidly obese patients, high resistin expression in serum is associated with hepatic steatosis, inflammation, and fibrosis. The development of elevated resistin expression may represent a link between obesity and the onset of steatohepatitis.
Similar content being viewed by others
References
Younossi ZM (2008) Review article: current management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Aliment Pharmacol Ther 28:2–12
Diehl AM (2010) Hepatic complications of obesity. Gastroenterol Clin N Am 39:57–68
Baranova A, Younossi ZM (2008) The future is around the corner: noninvasive diagnosis of progressive nonalcoholic steatohepatitis. Hepatology 47:373–375
Younossi ZM, Jarrar M, Nugent C, Randhawa M, Afendy M, Stepanova M, Rafiq N, Goodman Z, Chandhoke V, Baranova A (2008) A novel diagnostic biomarker panel for obesity-related nonalcoholic steatohepatitis (NASH). Obes Surg 18:1430–1437
Cheung O, Sanyal AJ (2010) Recent advances in nonalcoholic fatty liver disease. Curr 26:202–208
Edwards C, Hindle AK, Fu S, Brody F (2011) Downregulation of leptin and resistin expression in blood following bariatric surgery. Surg Endosc 25:1962–1968
Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu Y-C, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41:1313–1321
Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA (2001) The hormone resistin links obesity to diabetes. Nature 409:307–312
Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E, McCullough AJ, Forlani G, Melchionda N (1999) Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 107:450–455
Bertolani C, Sancho-Bru P, Failli P, Bataller R, Aleffi S, DeFranco R, Mazzinghi B, Romagnani P, Milani S, Gines P, Colmenero J, Parola M, Gelmini S, Tarquini R, Laffi G, Pinzani M, Marra F (2006) Resistin as an intrahepatic cytokine: overexpression during chronic injury and induction of proinflammatory actions in hepatic stellate cells. Am J Pathol 169:2042–2053
Pagano C, Soardo G, Pilon C, Milocco C, Basan L, Milan G, Donnini D, Faggian D, Mussap M, Plebani M, Avellini C, Federspil G, Sechi LA, Vettor R (2006) Increased serum resistin in nonalcoholic fatty liver disease is related to liver disease severity and not to insulin resistance. J Clin Endocrinol Metab 91:1081–1086
Singhal NS, Patel RT, Qi Y, Lee Y-S, Ahima RS (2008) Loss of resistin ameliorates hyperlipidemia and hepatic steatosis in leptin-deficient mice. Am J Physiol Endocrinol Metab 295:E331–E338
Tarkowski A, Bjersing J, Shestakov A, Bokarewa MI (2010) Resistin competes with lipopolysaccharide for binding to toll-like receptor 4. J Cell Mol Med 14:1419–1431
Pradere J-P, Troeger JS, Dapito DH, Mencin AA, Schwabe RF (2010) Toll-like receptor 4 and hepatic fibrogenesis. Semin Liver Dis 30:232–244
Testro AG, Visvanathan K (2009) Toll-like receptors and their role in gastrointestinal disease. J Gastroenterol Hepatol 24:943–954
Jiang L-L, Li L, Hong X-F, Li Y-M, Zhang B-L (2009) Patients with nonalcoholic fatty liver disease display increased serum resistin levels and decreased adiponectin levels. Eur J Gastroenterol Hepatol 21:662–666
Bajaj M, Suraamornkul S, Hardies LJ, Pratipanawatr T, DeFronzo RA (2004) Plasma resistin concentration, hepatic fat content, and hepatic and peripheral insulin resistance in pioglitazone-treated type II diabetic patients. Int J Obes Relat Metab Disord 28:783–789
Perseghin G, Lattuada G, De Cobelli F, Ntali G, Esposito A, Burska A, Belloni E, Canu T, Ragogna F, Scifo P, Del Maschio A, Luzi L (2006) Serum resistin and hepatic fat content in nondiabetic individuals. J Clin Endocrinol Metab 91:5122–5125
McTernan PG, Kusminski CM, Kumar S (2006) Resistin. Curr Opin Lipidol 17:170–175
Mattar SG, Velcu LM, Rabinovitz M, Barinas-Mitchell E, Eid GM, Ramanathan R, Taylor DS, Schauer PR (2005) Surgically-induced weight loss significantly improves nonalcoholic fatty liver disease and the metabolic syndrome. Ann Surg 242:610–617 discussion 618–620
Moschen AR, Molnar C, Wolf AM, Weiss H, Graziadei I, Kaser S, Ebenbichler CF, Stadlmann S, Moser PL, Tilg H (2009) Effects of weight loss induced by bariatric surgery on hepatic adipocytokine expression. J Hepatol 51:765–777
Kral JG, Thung SN, Biron S, Hould F-S, Lebel S, Marceau S, Simard S, Marceau P (2004) Effects of surgical treatment of the metabolic syndrome on liver fibrosis and cirrhosis. Surgery 135:48–58
Acknowledgement
Disclosures
Drs. Claire R. Edwards, A. Katharine Hindle, Patricia S. Latham, Sidney W. Fu, and Fred J. Brody have no conflict of interest or financial ties to disclose.
Author information
Authors and Affiliations
Corresponding author
Additional information
Funded by grants from the SAGES Foundation and a McCormick Center Genomics Pilot Grant.
Rights and permissions
About this article
Cite this article
Edwards, C.R., Hindle, A.K., Latham, P.S. et al. Resistin expression correlates with steatohepatitis in morbidly obese patients. Surg Endosc 27, 1310–1314 (2013). https://doi.org/10.1007/s00464-012-2603-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00464-012-2603-y