*Transcriptional Regulation by ERR and Its Role in NAFLD Pathogenesis DOI: http://dx.doi.org/10.5772/intechopen.109089*

insulin signal; a HFD model, which induces lipid transport into the liver; and a HCD model that induces *de novo* lipogenesis. ERR-PA also reversed the NASH phenotypes observed in the mice where NAFLD/NASH is developed due to loss of hepatic *Pten*. This evidence suggest that inhibiting ERR activity can serve as a viable approach to treat NAFLD/NASH development.

TGs are the primary content induced in NAFLD/NASH. TGs are synthesized via the glycerolipid biosynthesis pathway, where Glycerol-3-phosphate (G3P) and acyl-CoA is converted to LPA with the help of GPAT enzyme activity followed by incorporation into DAG and TG. Enzymes catalyzing the steps in this biosynthesis are subjected to regulations by ERR and other nuclear transcriptional factors. *Gpat1* null mice were found to have lower triacylglycerol and DAG concentrations and were protected from the HFD-induced insulin resistance, which was attributed to lower DAG-mediated PKCϵ activation [115]. Mice lacking GPAT3 expression had increased liver size with dysregulated cholesterol metabolism, implying that *Gpat3* plays a crucial role in regulating energy, glucose, and lipid levels [116]. GPAT4 is the major isoform in the liver and mammary gland [117]. Recent work has identified GPAT4 as a direct transcriptional target for ERRα and could be responsible for ERRα regulated NAFLD development [84].
