Rapid downregulation of adipose tissue lipoprotein lipase activity on food deprivation: evidence that TNF-alpha is involved.
When food was removed from young rats in the early morning, adipose tissue tumor necrosis factor (TNF)-alpha activity increased 50% and lipoprotein lipase (LPL) activity decreased 70% in 6 h. There was a strong negative correlation between the TNF-alpha and LPL activities. Exogenous TNF-alpha further decreased LPL activity. Pentoxifylline, known to decrease production of TNF-alpha, had no effect on LPL activity in fed rats but almost abolished the rise of TNF-alpha 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-alpha, indicating a shift in the LPL molecules toward an inactive state. Lipopolysaccharide increased adipose tissue TNF-alpha 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-alpha. We conclude that food deprivation, like lipopolysaccharide, signals via TNF-alpha 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.
Wu
Gengshu
G
Department of Medical Biosciences, Physiological Chemistry, University of Umeå, Sweden.
Brouckaert
Peter
P
Olivecrona
Thomas
T
D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D015536:Down-Regulation; D005508:Food Deprivation / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000502:physiology*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D008071:Lipoprotein Lipase