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

To assess the impact of PPARA activation on lncRNA expression and tissue specificity, Ppara wild-type mice (Ppara +/+ ) and Ppara-null mice (Ppara -/-) were treated with WY-14643 for 48 hours, and four tissues (liver, BAT, heart, muscle) then harvested for analysis. Cyp4a14 mRNA was markedly induced by WY-14643 in all four tissues and in a Ppara-dependent manner, as expected ( Figure 1C ). All six lncRNAs were induced in liver, including Gm15441, which exhibited >2000-fold increase in wild-type livers, > 10-fold higher than the other lncRNAs. In contrast to the induction of Cyp4a14 mRNA, lncRNA induction by WY-14643 was liver-specific, with no significant induction of the five other lncRNAs seen in BAT, heart, or muscle ( Figure LncRNA Gm15441 overlaps the coding region of Txnip, which is located on the opposing strand and also responds to WY-14643 treatment, albeit with different kinetics than Gm15441.