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Am J Physiol Endocrinol Metab 281: E957-E965, 2001;
0193-1849/01 $5.00
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Vol. 281, Issue 5, E957-E965, November 2001

Reduced body fat and increased hepatic lipid synthesis in mice bearing interleukin-6-secreting tumor

S. Metzger1, T. Hassin1, V. Barash2, O. Pappo3, and T. Chajek-Shaul1

1 Department of Medicine, Hadassah University Hospital, Mount Scopus, and Departments of 2 Biochemistry and 3 Pathology, Hadassah University Hospital, Ein Kerem, Jerusalem 91240, Israel

Chronic secretion of interleukin-6 (IL-6) in mice causes metabolic alteration in the liver, leading to increased synthesis of hepatic cholesterol and fatty acids (FA). Mice were injected with allogeneic tumor cells transduced with the murine IL-6 gene. During the 3 wk after tumor inoculation, elevated serum IL-6 levels were associated with increased spleen and liver weight. Histological examination of sections from the liver showed increased hepatocyte proliferation, resulting in liver enlargement. Body composition analysis revealed that IL-6 caused a significant loss in fat tissue without affecting lean body mass and water content. Hepatic de novo synthesis of FA and cholesterol, as measured by 3H2O incorporation, was three to five times as high in mice secreting IL-6 (IL-6 mice) as in pair-fed mice bearing nonsecreting tumors. This increase in FA and cholesterol synthesis is sufficient to maintain hepatic triglyceride secretion at levels comparable with those of pair-fed mice bearing nonsecreting tumors and, presumably, is the main source of cholesterol and FA-phospholipids necessary for hepatocyte proliferation.

hepatocyte proliferation; adipose tissue; fatty acids; cholesterol; triglyceride; glucose-6-phosphate dehydrogenase


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