OBJECTIVES: To investigate the influence of transmembrane tumor necrosis factor 
(TNF)-alpha on adipose tissue development and insulin-mediated glucose 
metabolism.
METHODS AND RESULTS: TNF-alpha and lymphotoxin-alpha-deficient mice expressing 
non-cleavable transmembrane TNF-alpha (Tg-tmTNF-alpha) and 
TNF-alpha/lymphotoxin-alpha double knockout (control) mice were kept on high-fat 
diet for 15 weeks. The food intake and feeding efficiency of Tg-tmTNF-alpha mice 
were significantly higher compared with control mice. At the end of the study, 
Tg-tmTNF-alpha mice had a significantly higher total body weight, as well as 
subcutaneous and gonadal adipose tissue mass. Histological analysis revealed 
that the expression of Tg-tmTNF-alpha resulted in a significantly increased 
adipocyte area and blood vessel density. Plasma leptin levels correlated 
positively with adipose tissue mass. The plasma levels of total cholesterol and 
HDL-cholesterol were significantly increased and LDL-cholesterol levels 
significantly decreased in Tg-tmTNF-alpha mice. Fasting blood glucose and plasma 
insulin levels were not different between the two genotypes and intraperitoneal 
glucose and insulin tolerance tests did not show significant differences.
CONCLUSIONS: Transmembrane TNF-alpha enhances adipose tissue formation without 
altering insulin-mediated glucose metabolism in mice with nutritionally induced 
obesity.