De novo lipogenesis pathway (DNL)

De novo lipogenesis is a metabolic pathway by which cells synthesize fatty acids from acetyl-CoA derived from non-lipid sources (mainly carbohydrates). This process occurs predominantly in the liver and adipose tissue and is tightly regulated by nutritional, hormonal, and transcriptional inputs. Under normal physiological conditions, DNL converts excess dietary carbohydrates into fatty acids, which are esterified into triglycerides for storage as a long-term energy reserve. Key enzymes in this pathway include ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FASN). While DNL is fundamental for energy homeostasis and cell survival, dysregulation or hyperactivity of DNL contributes to a spectrum of diseases, including obesity, type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease, cancer, and others. Pharmacological inhibition of DNL's core enzymes is an area of active therapeutic development.

Other names

De novo fatty acid synthesisDNLfatty acid biosynthesis pathway

Inhibition of fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), ATP-citrate lyase (ACLY), and citrate/isocitrate carrier (CIC) enzymes reduces endogenous fatty acid synthesis, thereby lowering lipid accumulation and impacting signaling processes