AJP - Gastrointestinal and Liver Physiology, Vol 268, Issue 3 451-G458, Copyright © 1995 by American Physiological Society

ARTICLES

Chronic iron overload causes activation of rat lipocytes in vivo

G. A. Ramm, S. C. Li, L. Li, R. S. Britton, R. O'Neill, Y. Kobayashi and B. R. Bacon
Department of Internal Medicine, Saint Louis University Health Sciences Center, Missouri 63110-0250.

Chronic iron overload can result in hepatic fibrosis and cirrhosis. Activated lipocytes, through increased production of collagen and extracellular matrix, play an important role in hepatic fibrogenesis in several types of experimental liver injury, but their contribution to hepatic injury after iron overload is unknown. This study examines the effect of iron overload on lipocyte activation, in vivo. Male Sprague-Dawley rats were fed a chow diet supplemented with 1% carbonyl iron for up to 20 mo. Controls were fed the chow diet alone. Lipocytes were prepared by sequential pronase and collagenase perfusion of the livers, followed by density-gradient centrifugation. Lipocyte activation was assessed by immunohistochemistry of liver sections and by Western blot analysis of alpha-smooth muscle actin expression in freshly isolated lipocytes. In addition, to measure the biosynthetic capability of these lipocytes, collagen and noncollagen protein production was determined after 3 days in culture, using [3H]proline incorporation. The hepatic iron concentration was increased by eightfold in the iron-loaded rats, and lipocytes from these animals expressed alpha-smooth muscle actin. Collagen production was increased by 2.5-fold, and noncollagen protein production was elevated by twofold in lipocytes isolated from iron-loaded rats. In the iron-loaded livers, autofluorescent material with the characteristics of lipofusion was present in periportal zones. Chronic iron overload expression results in the activation of lipocytes, as determined by increased expression of alpha-smooth muscle actin and by increased production of both collagen and noncollagen protein. This activation may contribute to iron-induced hepatic fibrogenesis.

This article has been cited by other articles:

				J. G. Parkes and D. M. Templeton Effects of Retinol and Hepatocyte-Conditioned Medium on Cultured Rat Hepatic Stellate Cells Ann. Clin. Lab. Sci., July 1, 2003; 33(3): 295 - 305. [Abstract] [Full Text] [PDF]

				G. A. Ramm, V. G. Nair, K. R. Bridle, R. W. Shepherd, and D. H. G. Crawford Contribution of Hepatic Parenchymal and Nonparenchymal Cells to Hepatic Fibrogenesis in Biliary Atresia Am. J. Pathol., August 1, 1998; 153(2): 527 - 535. [Abstract] [Full Text] [PDF]

				D K George, G A Ramm, L W Powell, L M Fletcher, N I Walker, L L Cowley, and D H G Crawford Evidence for altered hepatic matrix degradation in genetic haemochromatosis Gut, May 1, 1998; 42(5): 715 - 720. [Abstract] [Full Text] [PDF]

				J. E. Poulos, J. D. Weber, J. M. Bellezzo, A. M. Di Bisceglie, R. S. Britton, B. R. Bacon, and J. J. Baldassare Fibronectin and cytokines increase JNK, ERK, AP-1 activity, and transin gene expression in rat hepatic stellate cells Am J Physiol Gastrointest Liver Physiol, October 1, 1997; 273(4): G804 - G811. [Abstract] [Full Text] [PDF]