Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to metabolic stress

Chad N. Brocker; Donghwan Kim; Tisha Melia; Kritika Karri; Thomas J. Velenosi; Shogo Takahashi; Jessica A. Bonzo; David J. Waxman; Frank J. Gonzalez

Pathway analysis revealed that the WY-14643 upregulated genes are most highly enriched for the following biological processes: lipid metabolism, peroxisome, DNA replication, DNA repair, cell cycle and fatty acid oxidation ( Table S1D) . The downregulated genes are most highly enriched for: secreted factors, monooxygenase, immunity, serine protease inhibitor, metabolism of xenobiotics, and response to virus (Table S1E) . PPARA-dependent lncRNAs identified by RNA-seq were selected and mRNA levels monitored over a 24 hour period after WY-14643 treatment, revealing that lncRNA expression profiles paralleled those of known protein-coding PPARA target genes (Figure S1A-D) . As lncRNA expression is often highly tissue specific (Iwakiri et al., 2017; Melia et al., 2016; Perron et al., 2017) , the relative basal levels were measured for PPARA-responsive lncRNAs expressed in oxidative tissues that utilize fatty acids as an energy source and express PPARA at the highest levels. Ppara mRNA and its classic target gene Cyp4a14 served as controls. Basal levels of Cyp4a14 mRNA and intergenic lncRNAs ncRNA_chr19_15132 and ncRNA_chr4_3651 were highest in liver, while ncRNA_chr9_8249, ncRNA_chr9_8081, and 1300002E11Rik were most highly expressed in muscle. One of the PPARA-dependent lncRNAs, Gm15441, was also most highly expressed in brown adipose tissue (BAT) (Figure 1B) .