Influence of membrane-bound tumor necrosis factor (TNF)-alpha on obesity and glucose metabolism.
OBJECTIVE
To investigate the influence of transmembrane tumor necrosis factor (TNF)-alpha on adipose tissue development and insulin-mediated glucose metabolism.


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.
Voros
G
G
Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
Maquoi
E
E
Collen
D
D
Lijnen
H R
HR
D000273:Adipose Tissue / Q000187:drug effects / Q000503:physiopathology*; D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism*; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D017931:DNA Primers; D005951:Glucose Tolerance Test; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009765:Obesity / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology*
D001786:Blood Glucose; D017931:DNA Primers; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha