Impact of knockdown of the lncRNA 3930402G23Rik on gene expression profile of mouse liver in response to activation of PPARA by WY-14643.

Gene expression in livers of wild type adult male mice and in lncRNA 3930402G23Rik ("G23Rik") knockdown adult male mouse liver was assayed by RNA-seq, as part of a study of liver transcriptomic changes in response to activation of PPARA by WY-14,643, published in Molecular and Cellular Endocrinology (2022). These studies found that G23Rik-null mice were more susceptible to hepatic lipid accumulation in response to acute fasting. Histological analysis further revealed a pronounced buildup of lipid droplets and a significant increase in neutral triglycerides and lipids as indicated by enhanced oil red O staining of liver sections. Hepatic cholesterol, non-esterified fatty acid, and triglyceride levels were significantly elevated in G23Rik-null mice and associated with induction of the lipid-metabolism related gene Cd36. These findings provide evidence for a lncRNA dependent mechanism by which PPARA attenuates hepatic lipid accumulation in response to metabolic stress through lncRNA G23Rik induction. Twelve independent pools, comprised of RNA isolated from n=3-5 individual mouse livers per pool, were prepared and used for RNA-seq. Three pools were untreated, wild-type male mouse livers; three pools were WY-14,643-treated wild-type male mouse livers; three pools were untreated, lncRNA 3930402G23Rik-knockout male mouse livers; and three pools were WY-14,643-treated, lncRNA 3930402G23Rik-knockout mouse livers. Wy-14,643 treatment was given via the diet, at 0.1% for 48 hr.