The effect of tumor necrosis factor alpha on the activity of lipoprotein lipase in adipose tissue.
TNF alpha may play a critical role in many physiologic and pathophysiologic responses. It shows a bifunctional regulatory nature of both inhibiting tumor cell proliferation and enhancing growth and differentiation of other cells. TNF alpha acts as a mediator, binding to specific high affinity receptors to elicit biological responses. TNF alpha may be an essential local and systemic mediator in the pathogenesis of cachexia. By inhibiting the activity of lipogenic enzymes, it affects lipid mobilization from adipose tissue and adipocyte differentiation. The ability of TNF alpha to inhibit anabolic processes in adipocytes and preadipocytes is not unique and has been displayed, though to a lesser degree, by other cytokines such as LT, IFN-gamma, and IL-1. In infected animals, the effect of TNF alpha on LPL of inhibiting anabolic processes and enhancing secretion of FFA by adipocytes, may be important in providing additional energy needed by the immune system to combat invasion. However, the relationship between the suppression of the anabolic processes and the cytotoxicity is uncertain and prolonged action may lead to wasting. The evidence suggests that in the adipocyte, TNF alpha is the unique molecule that suppresses LPL through the selective inhibition of mRNA production. As a consequence of the decrease in the enzyme amounts, there is a reduction in TG-uptake and lipid deposition contributing to cachexia. Neutralizing the action of TNF alpha may reverse the cachectic processes and potentially improve the condition. Further research into the induction, synthesis and regulation of TNF alpha production is necessary. Modern molecular biology techniques should serve as useful models in understanding the regulation of TNF alpha functions in response to stimuli. Development of faster and more sensitive detection methods would improve the measurement of the low concentrations of cytokines.
Porat
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Department of Immunology, McMaster University, Hamilton, Ontario, Canada.
D000273:Adipose Tissue / Q000166:cytology / Q000201:enzymology*; D000818:Animals; D002454:Cell Differentiation; D015536:Down-Regulation; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D008071:Lipoprotein Lipase