Interferons and Tumor Necrosis Factors Have Similar Catabolic Effects on 3T3 L1 Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 83; no. 21; pp. 8313 - 8317
• Main Authors: Patton, John S., Shepard, H. Michael, Wilking, Helga, Lewis, Gail, Aggarwal, Bharat B., Eessalu, Thomas E., Gavin, Lawrence A., Grunfeld, Carl
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01.11.1986; National Acad Sciences
• Subjects: Acetates - metabolism; Adipocytes; Adipose Tissue - metabolism; Animals; Cell Survival - drug effects; Cells, Cultured; Cytokines; Deoxyglucose - metabolism; Fatty Acids - metabolism; Fibroblasts; Fibroblasts - metabolism; Glycoproteins - metabolism; Glycoproteins - pharmacology; Infections; Interferons - pharmacology; Lipid Metabolism; Lipids; Lipoprotein Lipase - analysis; Mice; Nonesterified fatty acids; Receptors; Recombinant Proteins - pharmacology; Triglycerides; Tumor Necrosis Factor-alpha
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.83.21.8313

The effect of a variety of cytokines on lipid metabolism in 3T3 L1 mouse fibroblasts and adipocytes was studied. Uptake of [3H]acetate by adipocytes and heparin-releasable lipoprotein lipase activity was inhibited after treatments of the cells with picomolar concentrations of recombinant human tumor necrosis factor α (rHuTNF-α ), human tumor necrosis factor β (rHuTNF-β , also called lymphotoxin), murine interferon-γ (rMuIFN-γ ), and a human hybrid interferon-α [rHuIFN-α2/α1(Bgl II)]. Recombinant human interferon-γ (rHuIFN-γ ), natural human colony-stimulating factor (HuCSF), and human interleukin 2 (HuIL-2) had no effect. Similar though less-marked suppression of [3H]acetate uptake by cytokines was seen in 3T3 L1 fibroblasts. Cytokines inhibited the incorporation of [3H]acetate into both membrane and storage lipids in the adipocytes. In addition to blocking lipid uptake and synthesis, rHuTNF-α and -β , and rMuIFN-γ stimulated the release of free fatty acid into the medium from adipocytes. Binding studies suggest that rHuTNF-α and rHuTNF-β compete for the same cell-surface receptor on 3T3 L1 adipocytes, while rMuIFN-γ binds to a separate receptor. The binding of rTNF-α to both adipocytes and fibroblasts can be significantly enhanced by preexposure of the cells to rMuIFN-γ . There appear to be both high- and low-affinity receptors for rHuTNF-α on adipocytes, whereas fibroblasts exhibit a single class of high-affinity receptors. These results suggest that a variety of structurally distinct cytokines possess lipid mobilization activity, which may be of critical importance to the host in defense against infection or malignancy.