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

Abstract

When food was removed from young rats in the early morning, adipose tissue tumor necrosis factor (TNF)-α activity increased 50% and lipoprotein lipase (LPL) activity decreased 70% in 6 h. There was a strong negative correlation between the TNF-α and LPL activities. Exogenous TNF-α further decreased LPL activity. Pentoxifylline, known to decrease production of TNF-α, had no effect on LPL activity in fed rats but almost abolished the rise of TNF-α and 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-α, indicating a shift in the LPL molecules toward an inactive state. Lipopolysaccharide increased adipose tissue TNF-α and 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-α. We conclude that food deprivation, like lipopolysaccharide, signals via TNF-α to 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.