Fig. 7.

Mechanism of GDNF prevention of hepatic steatosis. GDNF signaling in hepatocytes through its receptors supressess gene expression and protein levels of transcription factors, including PPAR-γ, PPAR-α, and Srebf1. This leads to reductions in gene expression and protein levels of their targets, which include lipid membrane transporters such as CD36 and carnitine palmitoyl-transferase 1a (Cpt1a) and enzymes that catalyze triglyceride synthesis during de novo lipogenesis such as fatty acid synthase (Fasn), stearoyl-coenzyme A desaturase 1 (Scd1), and diacylglycerol O-acyltransferase 2 (Dgat2). Green arrows indicate pathways that increase or decrease intracellular fatty acid and triglyceride levels in hepatocytes. Black arrows indicate gene transcriptional processes. Processes that are downregulated by GDNF are shown by a red arrow facing downward. DAG, diacylglycerol; FA, fatty acid.