Elevated resistin levels in cirrhosis are associated with the proinflammatory state and altered hepatic glucose metabolism but not with insulin resistance

• Published in: American journal of physiology: endocrinology and metabolism 2006-08, Vol.291 (2), p.E199-E206
• Main Authors: Bahr, Matthias J, Ockenga, Johann, Boker, Klaus H. W, Manns, Michael P, Tietge, Uwe J. F
• Format: Article
• Language: English
• Subjects: Biomarkers - metabolism; Cytokines - blood; Female; Glucose - metabolism; Humans; Inflammation Mediators - metabolism; Insulin Resistance; Liver - metabolism; Liver Cirrhosis - blood; Male; Middle Aged; Resistin - blood
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00291.2005

1 Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany; 2 Department of Gastroenterology, Hepatology, and Endocrinology, Charité Campus Mitte, Berlin, Germany; and 3 Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands Submitted 28 June 2005 ; accepted in final form 6 February 2006 The adipokine resistin has been implicated in obesity and insulin resistance. Liver cirrhosis is associated with decreased body fat mass and insulin resistance. We determined plasma resistin levels in 57 patients with cirrhosis, 13 after liver transplantation, and 30 controls and correlated these with hemodynamic as well as hepatic and systemic metabolic parameters. Patients with cirrhosis had, dependent on the clinical stage, an overall 86% increase in resistin levels ( P < 0.001) with hepatic venous resistin being higher than arterial levels ( P < 0.001). Circulating resistin was significantly correlated with plasma TNF- levels ( r = 0.62, P < 0.001). No correlation was observed between resistin and hepatic hemodynamics, body fat mass, systemic energy metabolism, and the degree of insulin resistance. However, plasma resistin in cirrhosis was negatively associated with hepatic glucose production ( r = –0.47, P < 0.01) and positively with circulating free fatty acids (FFA; r = 0.40, P < 0.01) and ketone bodies ( r = 0.48, P < 0.001) as well as hepatic ketone body production ( r = 0.40, P < 0.01). After liver transplantation, plasma resistin levels remained unchanged, whereas insulin resistance was significantly improved ( P < 0.01). These data provide novel insights into the role of resistin in the pathophysiological background of a catabolic disease in humans and also indicate that resistin inhibition may not represent a suitable therapeutic strategy for the treatment of insulin resistance and diabetes in patients with liver cirrhosis. hepatic turnover; body composition; liver; portal pressure Address for reprint requests and other correspondence: U. Tietge, Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, Univ. Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands (e-mail: u_tietge{at}yahoo.com )