TNFalpha interferes with adaptation to starvation and activates pro-atherogenic processes

Pathenogenesis of atherosclerosis results from the interactions between disrupted lipid homeostasis and immune response, but the molecular bridges between the major players are still a matter of controversy. We performed a systemic study of the imflammatory cytokine tumor necrosis factor alpha (TNF alpha), a well established anorexia agent, in the livers of the mice exposed to 20h-cytokine/starvation. We show that treatment with TNF-alpha reverses adaptations to fasting. Moreover, it up-regulates cholesterol biosynthesis and down-regulates bile acids synthesis, which leads to disrupted cholesterol homeostasis and pro-atherogenic changes. Interestingly, we found that TNF alpha also interferes with gene regulation of the xenobiotic metabolism. Keywords: treatment and diet effects Mice have been either saline treated (nontreated group), saline treated and fasted for 20h (fasted group), and TNF-alpha treated (30 mikrograms per animal) and fasted for 20h (TNF-alpha group). 3 biological replicas from fasted and TNF-alpha groups were co-hybridized with pool of nontreated group. No dye-swaps were performed.