July 1, 1987Open Access
Tumor necrosis factor-alpha stimulates hepatic lipogenesis in the rat in vivo.
Key Result
Tumor necrosis factor-alpha administration in rats increased plasma triglycerides 2.2-fold within 2 hours and significantly stimulated hepatic fatty acid and sterol synthesis.
Structured PICO
Does tumor necrosis factor-alpha stimulate hepatic lipogenesis in rats in vivo?
P
Population
Rats (in vivo model)
I
Intervention
Tumor necrosis factor-alpha (25 micrograms/200 g)
O
Outcome
Hepatic lipogenesis (lipid synthesis, plasma triglycerides, plasma cholesterol)surrogate
Tumor necrosis factor-alpha rapidly stimulates hepatic lipogenesis in vivo, suggesting a mechanism for the hyperlipidemia observed during infections.
Main Result
Effect estimate: 2.2-fold increase
Absolute Event Rate: 113.4% vs 51.8%
p-value: p=<0.01
Limitations
- Animal model results may not fully translate to human pathology
- The exact mechanism by which TNF increases hepatic lipid synthesis (direct action vs. induction of other cytokines) was not elucidated
Abstract
The hyperlipidemia accompanying infection has been attributed to production of tumor necrosis factor. This cytokine inhibits adipose tissue lipoprotein lipase, which could decrease clearance of lipoproteins. Infections also increase hepatic lipogenesis. We now have demonstrated that tumor necrosis factor-alpha stimulates lipid synthesis in vivo. 2 h after administration of tumor necrosis factor (25 micrograms/200 g), plasma triglycerides increase 2.2-fold and remain elevated for 17 h. Plasma cholesterol also increases, but this effect appears after 7 h. Tumor necrosis factor rapidly stimulates incorporation of tritiated water into fatty acids in the liver (1-2 h), which persists for 17 h. Also, tumor necrosis factor stimulates hepatic sterol synthesis. Of note, tumor necrosis factor treatment does not stimulate lipid synthesis in other tissues, including adipose tissue. Labeled fatty acids rapidly increase in the plasma, raising the possibility that stimulation of hepatic lipogenesis by tumor necrosis factor contributes to the hyperlipidemia of infection.