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Loss of TNFR1 up‐regulates hepatic SIRT1 expression: possible role of micro inhibitory RNA processing factor DICER
Author(s) -
Gearhart Kylie,
Menio Jade E,
Wheeler Michael D
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.740.8
Subject(s) - dicer , microbiology and biotechnology , inhibitory postsynaptic potential , rna processing , microrna , rna , chemistry , biology , rna interference , neuroscience , biochemistry , gene
We recently demonstrated the central innate immune cytokine tumor necrosis factor, TNFα, significantly down‐regulates hepatic SIRT1, a key regulator of hepatic metabolism and circadian control. It is hypothesized that SIRT1 may be suppressed by micro‐inhibitory RNAs (miRNA), specifically miR‐138, which are small non‐coding RNAs that control gene expression at the translational level. The specific hypothesis is that TNFα upregulates microRNA production, miR‐138 in particular, by activating the RNase III‐like enzyme Dicer and suppressing SIRT1. Since fasting has been shown to stimulate SIRT1 expression in the liver, Wild type mice and TNFR1−/− mice were fasted overnight. In the absence of TNF signaling in the TNFR1−/− mice, SIRT1 expression was increased whereas dicer expression and miR‐138 levels were blunted compared to wildtype mice. These data highlight an important mechanism for immune regulation hepatic metabolism and possible disruption of the circadian control pathway.