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

Long non-coding RNAs (lncRNAs) act as regulators of gene expression and play important regulatory roles in many metabolic processes. For example, lncRNA Blnc1 works in concert with another important hepatic nuclear receptor, liver X receptor (LXR), to activate the lipogenic gene program (Zhao et al., 2018) . Down-regulation of lncRNA lncOb reduces leptin, leading to a leptin responsive form of obesity (Dallner et al., 2019) . Other studies found that lncRNAs are regulated during adipocyte differentiation (Yuan et al., 2019a; Yuan et al., 2019b) , are expressed in liver in a sex-dependent manner when regulated by growth hormone (Melia et al., 2016; Melia and Waxman, 2019) , and can be strongly induced by xenobiotic exposure (Lodato et al., 2017) . A compartment-specific transcriptional profiling approach revealed that lncRNA PAXIP1-AS1 regulates pulmonary arterial hypertension by modulating smooth muscle cell function (Jandl et al., 2019) . Further, lncRNA HOTAIR influences glucose metabolism by upregulation of GLUT1 in hepatocellular carcinoma cells (Wei et al., 2017) . It is therefore reasonable to consider that lncRNAs may play important roles in the metabolic remodeling and anti-inflammatory actions that occur after PPARA activation.