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Diabetes 53:74-81, 2004
© 2004 by the American Diabetes Association, Inc.

Stimulation of Lipolysis by Tumor Necrosis Factor-{alpha} in 3T3-L1 Adipocytes Is Glucose Dependent

Implications for Long-Term Regulation of Lipolysis

Allan Green1, John M. Rumberger1, Charles A. Stuart2, and Mary S. Ruhoff1

1 Bassett Research Institute, Bassett Healthcare, Cooperstown, New York
2 Department of Internal Medicine, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee

Tumor necrosis factor-{alpha} (TNF-{alpha}) and hyperglycemia both impair insulin sensitivity in vivo. This may be secondary to stimulation of adipose tissue lipolysis and consequent increased circulating free fatty acids (FFAs). Here we report that neither TNF-{alpha} nor glucose alone has a pronounced effect on lipolysis in 3T3-L1 adipocytes. However, the combination of TNF-{alpha} plus glucose markedly stimulates lipolysis. Glucose does not affect the ability of isoproterenol to stimulate lipolysis. Alternative substrates such as acetate, pyruvate, and lactate do not allow the TNF-{alpha} effect. Mannose was almost as effective as glucose; fructose was marginally effective, but galactose was ineffective. The effectiveness of the sugars corresponded with production of lactate, i.e., the cells readily produced lactate from glucose or mannose, slightly from fructose, and not at all from galactose. The ability of TNF-{alpha} to phosphorylate extracellular signal-regulated kinase 1 (ERK1) and ERK2 and to downregulate perilipin (which has been implicated in the lipolytic effect of TNF-{alpha}) was not affected by glucose. We conclude that the lipolytic action of TNF-{alpha} is influenced by glucose in 3T3-L1 adipocytes. The findings suggest that glucose metabolism is required for the lipolytic response to TNF-{alpha} but not for early signaling events. These findings suggest novel mechanisms by which TNF-{alpha} and hyperglycemia raise FFA levels and induce insulin resistance.


Address correspondence and reprint requests to Allan Green, Ph.D., Bassett Research Institute, Bassett Healthcare, One Atwell Road, Cooperstown, NY 13326. E-mail: allan.green{at}bassett.org


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Copyright © 2004 by the American Diabetes Association.