Reduced body fat and increased hepatic lipid synthesis in mice bearing interleukin-6-secreting tumor.
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 (3)H(2)O 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.
Metzger
S
S
Department of Medicine, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel.
Hassin
T
T
Barash
V
V
Pappo
O
O
Chajek-Shaul
T
T
D000273:Adipose Tissue; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D002455:Cell Division; D002784:Cholesterol / Q000096:biosynthesis / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D005227:Fatty Acids / Q000096:biosynthesis; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism; D015870:Gene Expression; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D022781:Hepatocytes / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008055:Lipids / Q000096:biosynthesis*; D008071:Lipoprotein Lipase / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D014162:Transfection; D014280:Triglycerides / Q000097:blood; D014407:Tumor Cells, Cultured
D001786:Blood Glucose; D008076:Cholesterol, HDL; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D015850:Interleukin-6; D008055:Lipids; D014280:Triglycerides; D002784:Cholesterol; D005954:Glucosephosphate Dehydrogenase; D008071:Lipoprotein Lipase