ANTITUMOR NECROSIS FACTOR-ALPHA TREATMENT INTERFERES WITH CHANGES IN LIPID-METABOLISM IN A TUMOR CACHEXIA MODAL

1. Rats bearing the Yoshida ascites hepatoma AH-130 showed an importan t decrease in white adipose tissue lipoprotein lipase activity as comp ared with non-tumour bearing rats. This was associated with a lower ad ipose tissue mass, as estimated from the weight of the lumbar fat-pads . Conversely, lipoprotein lipase activity was markedly increased in br own adipose tissue and heart. 2. These changes were associated with a distinct hyperlipaemia, essentially manifested as an increase in circu lating triacylglycerol levels, whereas no changes were observed in gly caemia. 3. Tumour-bearing rats were treated with a polyclonal anti-mur ine tumour necrosis factor-alpha antibody or with a non-immune IgG pre paration. Control animals were either untreated or received a nonimmun e IgG preparation, Anti-tumour necrosis factor-alpha treatment resulte d in a significant increase in lipoprotein lipase activity in white ad ipose tissue in animals bearing a tumour growing exponentially (day 4 after inoculation) as compared with the animals receiving a non-immune goat IgG preparation. In addition, animals bearing an stationary tumo ur (day 7 after inoculation) and submitted to anti-tumour necrosis fac tor-alpha treatment had a higher adipose tissue lipoprotein lipase act ivity as compared with the IgG- or the non-treated groups. Correspondi ngly, circulating triacylglycerol levels were markedly decreased, with a lower hyperlipaemia than in control tumour-bearing rats. 4. These o bservations suggest that tumour necrosis factor-alpha is involved in a ctivating the lipid metabolic changes that develop in rats after trans plantation of a fast-growing tumour.