LIPID-METABOLISM IN TUMOR-BEARING MICE - STUDIES WITH KNOCKOUT MICE FOR TUMOR-NECROSIS-FACTOR RECEPTOR-1 PROTEIN

The implantation of the Lewis lung carcinoma (a fast-growing mouse tum our that induces cachexia) to both wild-type and gene-deficient mice f or the tumour necrosis factor (TNF) receptor type I protein (Tnfr1 deg rees/Tnfr1 degrees), resulted in a considerable loss of carcass (26%) and white (77%) and brown adipose (37%) tissue weights in the wild-typ e mice, while it induced much less marked effects in the gene-deficien t mice. Tumour burden also inflicted an important decrease in total li poprotein lipase (LPL) activity in epididymal white adipose tissue (50 %) in the wild-type mice while no changes were observed in the knockou t mice. In addition, all tumour-bearing animals were clearly hypertrig lyceridaemic (80% increase in circulating triacylglycerols in wild-typ e and 36% in knockout mice). It is concluded that although TNF seems t o be to some extent responsible for adipose waste, LPL changes and hyp erlipaemia (via receptor I), the role of other cytokines (alone or in combination with TNF) in promoting changes in lipid metabolism during cancer cachexia cannot be discarded. (C) 1997 Elsevier Science Ireland Ltd.