Rapid downregulation of adipose tissue lipoprotein lipase activity on food deprivation: evidence that TNF- is involved

Wu, Gengshu, Peter Brouckaert, and Thomas Olivecrona. Rapid downregulation of adipose tissue lipoprotein lipase activity on food deprivation: evidence that TNFis involved. Am J Physiol Endocrinol Metab 286: E711–E717, 2004. First published December 23, 2003; 10.1152/ajpendo.00257.2003.—When food was removed from young rats in the early morning, adipose tissue tumor necrosis factor (TNF)activity increased 50% and lipoprotein lipase (LPL) activity decreased 70% in 6 h. There was a strong negative correlation between the TNFand LPL activities. Exogenous TNFfurther decreased LPL activity. Pentoxifylline, known to decrease production of TNF, had no effect on LPL activity in fed rats but almost abolished the rise of TNFand the decrease of LPL activity in rats deprived of food. The specific activity of LPL decreased from 0.92 mU/ng in fed rats to 0.35 and 0.24 mU/ng in rats deprived of food given saline or TNF, indicating a shift in the LPL molecules toward an inactive state. Lipopolysaccharide increased adipose tissue TNFand decreased LPL activity. Both of these effects were strongly impeded by pretreatment of the rats with pentoxifylline, or dexamethasone. Pretreatment of the rats with actinomycin D virtually abolished the response of LPL activity to food deprivation or exogenous TNF. We conclude that food deprivation, like lipopolysaccharide, signals via TNFto a gene whose product causes a rapid shift of newly synthesized LPL molecules toward an inactive form and thereby shuts down extraction of lipoprotein triglycerides by the adipose tissue.