Anti-tumour necrosis factor-alpha treatment interferes with changes in lipid metabolism in a tumour cachexia model.
1. Rats bearing the Yoshida ascites hepatoma AH-130 showed an important decrease in white adipose tissue lipoprotein lipase activity as compared with non-tumour bearing rats. This was associated with a lower adipose tissue mass, as estimated from the weight of the lumbar fat-pads. Conversely, lipoprotein lipase activity was markedly increased in brown adipose tissue and heart. 2. These changes were associated with a distinct hyperlipaemia, essentially manifested as an increase in circulating triacylglycerol levels, whereas no changes were observed in glycaemia. 3. Tumour-bearing rats were treated with a polyclonal anti-murine tumour necrosis factor-alpha antibody or with a non-immune IgG preparation. Control animals were either untreated or received a non-immune IgG preparation. Anti-tumour necrosis factor-alpha treatment resulted in a significant increase in lipoprotein lipase activity in white adipose 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 tumour (day 7 after inoculation) and submitted to anti-tumour necrosis factor-alpha treatment had a higher adipose tissue lipoprotein lipase activity as compared with the IgG- or the non-treated groups. Correspondingly, circulating triacylglycerol levels were markedly decreased, with a lower hyperlipaemia than in control tumour-bearing rats. 4. These observations suggest that tumour necrosis factor-alpha is involved in activating the lipid metabolic changes that develop in rats after transplantation of a fast-growing tumour.
Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Spain.
N
N
Carbó
P
P
Costelli
L
L
Tessitore
G J
GJ
Bagby
F J
FJ
López-Soriano
F M
FM
Baccino
J M
JM
Argilés
D000273:Adipose Tissue / Q000201:enzymology*; D000818:Animals; D001323:Autoantibodies / Q000008:administration & dosage*; D002100:Cachexia / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000008:administration & dosage; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000097:blood / Q000378:metabolism*; D051381:Rats; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D001323:Autoantibodies; D007074:Immunoglobulin G; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D008071:Lipoprotein Lipase