Hepatic lipid synthesis pathway

The "hepatic lipid synthesis pathway" refers broadly to the network of biochemical reactions responsible for synthesizing fatty acids and complex lipids within hepatocytes. This includes uptake/export of fatty acids from circulation, de novo lipogenesis from carbohydrates via acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), desaturation/elongation by stearoyl-CoA desaturase 1 (SCD1), esterification into triglycerides/cholesteryl esters/diglycerides/phospholipids—followed by storage in cytoplasmic droplets or export as very low-density lipoproteins. The process is tightly regulated at multiple levels by hormones/nutrients through signaling pathways involving AMPK/AKT/mTORC/SREBP/PPARs/LXR/FXR/HNF4α among others. Dysregulation leads to pathological fat accumulation seen in NAFLD/NASH/metabolic syndrome/cardiovascular diseases. While individual components are drug targets—such as ACC/FAS/SCD1/PPARα—the overall "hepatic lipid synthesis pathway" is not itself a discrete molecular target but rather an integrated metabolic system composed of many interacting proteins and regulatory elements.

Other names

Hepatic lipid metabolism pathwayLiver lipid synthesis pathwayDe novo lipogenesis (in liver)Hepatic de novo lipogenesis

Drugs targeting the hepatic lipid synthesis pathway act by modulating key enzymes or transcription factors involved in fatty acid and triglyceride biosynthesis, oxidation, or export. Mechanisms include inhibition of de novo lipogenesis enzymes, activation of nuclear receptors to promote β‑oxidation or reduce triglyceride accumulation, and modulation of transcriptional regulators such as SREBP1c or ChREBP.