Tg. Kirchgessner et al., TUMOR-NECROSIS-FACTOR-ALPHA CONTRIBUTES TO OBESITY-RELATED HYPERLEPTINEMIA BY REGULATING LEPTIN RELEASE FROM ADIPOCYTES, The Journal of clinical investigation, 100(11), 1997, pp. 2777-2782
Cytokines, in particular tumor necrosis factor-alpha (TNF-alpha), have
significant effects on energy metabolism and appetite although their
mechanisms of action are largely unknown. Here, we examined whether TN
F-alpha modulates the production of leptin, the recently identified fa
t-specific energy balance hormone, in cultured adipocytes and in mice.
TNF-alpha treatment of 3T3-L1 adipocytes resulted in rapid stimulatio
n of leptin accumulation in the media, with a maximum effect at 6 h, T
his stimulation was insensitive to cycloheximide, a protein synthesis
inhibitor, but was completely inhibited by the secretion inhibitor bre
feldin A, indicating a posttranslational effect. Treatment of mice wit
h TNF-alpha also caused a similar increase in plasma leptin levels. Fi
nally, in obese TNF-alpha-deficient mice, circulating leptin levels we
re significantly lower, whereas adipose tissue leptin was higher compa
red with obese wild-type animals. These data provide evidence that TNF
-alpha can act directly on adipocytes to regulate the release of a pre
formed pool of leptin, Furthermore, they suggest that the elevated adi
pose tissue expression of TNF-alpha that occurs in obesity may contrib
ute to obesity-related hyperleptinemia.