Iron in fatty liver and in the metabolic syndrome: a promising therapeutic target

Articles in Press

Paola Dongiovanni, Anna Ludovica Fracanzani, Silvia Fargion, Luca Valenti

Received 22 February 2011; received in revised form 29 May 2011; accepted 31 May 2011. published online 20 June 2011.
Accepted Manuscript

Abstract

The dysmetabolic iron overload syndrome (DIOS) is now a frequent finding in the general population, as is detected in about one third of patients with nonalcoholic fatty liver disease (NAFLD) and the metabolic syndrome. The pathogenesis is related to altered regulation of iron transport associated with steatosis, insulin resistance, and subclinical inflammation, often in the presence of predisposing genetic factors. Evidence is accumulating that excessive body iron plays a causal role in insulin resistance through still undefined mechanisms, that probably involve a reduced ability to burn carbohydrates and altered function of adipose tissue. Furthermore, DIOS may facilitate the evolution to type 2 diabetes by altering beta-cell function, the progression of cardiovascular disease by contributing to the recruitment and activation of macrophages within arterial lesions, and the natural history of liver disease by inducing oxidative stress in hepatocytes, activation of hepatic stellate cells, and malignant transformation by promotion of cell growth and DNA damage.

Based on these premises, the association among DIOS, metabolic syndrome, and NAFLD is being investigated as a new risk factor to predict the development of overt cardiovascular and hepatic diseases, and possibly hepatocellular carcinoma, but most importantly, represents also a treatable condition. Indeed, iron depletion, most frequently achieved by phlebotomy, has been shown to decrease metabolic alterations and liver enzymes in controlled studies in NAFLD. Additional studies are warranted to evaluate the potential of iron reductive therapy on hard clinical outcomes in patients with DIOS.

Keywords: Iron, Insulin Resistance, Nonalcoholic Fatty Liver Disease, Metabolic Syndrome, Vascular Damage, Hereditary Hemochromatosis, Nonalcoholic Steatohepatitis, Oxidative Stress

No full text is available. To read the body of this article, please view the PDF online.

Department of Internal Medicine, Centro Malattie Metaboliche del Fegato, Università degli Studi di Milano, and Fondazione IRCCS “Ca’ Granda” Ospedale Maggiore Policlinico, Milan, Italy

PII: S0168-8278(11)00442-9
doi:10.1016/j.jhep.2011.05.008
© 2011 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.

Source