Review
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World J Hepatol. Apr 27, 2012; 4(4): 129-138
Published online Apr 27, 2012. doi: 10.4254/wjh.v4.i4.129
G6PT-H6PDH-11βHSD1 triad in the liver and its implication in the pathomechanism of the metabolic syndrome
Ibolya Czegle, Miklós Csala, József Mandl, Angelo Benedetti, István Karádi, Gábor Bánhegyi
Ibolya Czegle, István Karádi, 3rd Department of Internal Medicine, Semmelweis University, 1125 Budapest, Hungary
Ibolya Czegle, József Mandl, Pathobiochemistry Research Group, Hungarian Academy of Sciences, 1094 Budapest, Hungary
Miklós Csala, József Mandl, Gábor Bánhegyi, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, 1094 Budapest, Hungary
Angelo Benedetti, Gábor Bánhegyi, Department of Pathophysiology, Experimental Medicine and Public Health, University of Siena, 53100 Siena, Italy
Author contributions: Czegle I performed the underlying research; Mandl J, Benedetti A and Bánhegyi G designed the research; Czegle I, Csala M, Mandl J, Benedetti A, Karádi I and Bánhegyi G analyzed the literature and wrote the paper.
Supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences to Csala M
Correspondence to: Gábor Bánhegyi, MD, PhD, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, 1444 Budapest, PO Box 260, Hungary. banhegyi@eok.sote.hu.
Telephone: +36-1-4591500 Fax: +36-1-2662615
Received: May 5, 2011
Revised: November 16, 2011
Accepted: April 24, 2012
Published online: April 27, 2012
Abstract

The metabolic syndrome, one of the most common clinical conditions in recent times, represents a combination of cardiometabolic risk determinants, including central obesity, glucose intolerance, insulin resistance, dyslipidemia, non-alcoholic fatty liver disease and hypertension. Prevalence of the metabolic syndrome is rapidly increasing worldwide as a consequence of common overnutrition and consequent obesity. Although a unifying picture of the pathomechanism is still missing, the key role of the pre-receptor glucocorticoid activation has emerged recently. Local glucocorticoid activation is catalyzed by a triad composed of glucose-6-phosphate-transporter, hexose-6-phosphate dehydrogenase and 11β-hydroxysteroid dehydrogenase type 1 in the endoplasmic reticulum. The elements of this system can be found in various cell types, including adipocytes and hepatocytes. While the contribution of glucocorticoid activation in adipose tissue to the pathomechanism of the metabolic syndrome has been well established, the relative importance of the hepatic process is less understood. This review summarizes the available data on the role of the hepatic triad and its role in the metabolic syndrome, by confronting experimental findings with clinical observations.

Keywords: Metabolic syndrome, Liver, Glucocorticoid, Glucose-6-phosphate-transporter, Hexose-6-phosphate dehydrogenase, 11β-hydroxysteroid dehydrogenase type 1