FASN

Overview

FASN encodes fatty acid synthase, a key lipogenic enzyme that catalyzes the de novo synthesis of long-chain fatty acids. In normal physiology, FASN contributes to membrane biogenesis, energy storage, and lipid signaling, but its expression is often tightly regulated because excessive lipogenesis can support metabolic dysfunction and disease. As a result, FASN is widely studied as a metabolic node linking nutrient availability, lipid homeostasis, and cellular growth.

In biomedical research, FASN is frequently examined in the context of cancer and metabolic disease because many tumors and lipid-disordered tissues show increased dependence on de novo lipogenesis. Its activity is commonly discussed alongside pathways such as SIRT1/AMPK, SREBP-1c, PPARG, and mTOR, reflecting its position downstream of broader metabolic signaling networks. In recent studies, FASN has been investigated both as a disease-associated biomarker and as a therapeutic target, including in colorectal cancer, hepatocellular carcinoma, and fatty liver-related models.

Focus of Latest Publications

Recent publications have focused on FASN as a metabolic and therapeutic target across cancer and liver disease models. In hepatocellular carcinoma, FASN was identified among cholesterol homeostasis genes that were differentially expressed in TCGA data, where it was upregulated alongside several other lipid-related genes. Although FABP5 and ADH4 emerged as the main independent prognostic markers, the study placed FASN within a broader cholesterol and lipid metabolism signature associated with HCC biology and risk stratification.

Several studies examined FASN in the context of hepatic lipid metabolism and steatotic liver disease. In a mouse and HepG2 cell model of non-alcoholic fatty liver disease, Swertia mussotii treatment activated the SIRT1/AMPK axis and downregulated FASN, ACC, and SREBP-1c, consistent with reduced de novo lipogenesis and improved lipid accumulation, inflammation, and oxidative stress. In a separate study of metabolic dysfunction–associated steatotic liver disease, the novel inhibitor 84-B10 directly bound the MAT domain of FASN, inhibited its enzymatic activity, and promoted TRIM28-dependent ubiquitination and proteasomal degradation of FASN. This was associated with reduced lipid accumulation and mitochondrial dysfunction in hepatocytes and improved hepatic metabolic alterations and steatosis in HFD-fed mice.

FASN was also investigated in colorectal cancer as a mediator of treatment response. Using samples from a window trial of the FASN inhibitor TVB-2640, along with colon cancer cell lines and patient-derived organoids, investigators found that FASN inhibition induced DNA damage but impaired the DNA damage response. Mechanistically, FASN inhibition altered histone acetylation, reduced ATM expression and CHK2 phosphorylation, and limited BRCA1 and ATM recruitment to γH2AX foci. These effects potentiated chemotherapy-induced double-strand breaks and apoptotic cell death, and created synthetic lethality with PARP inhibition.

Overall, the recent literature portrays FASN as a central node in lipid synthesis with relevance to liver metabolism and tumor biology. Across these studies, FASN suppression was linked to reduced lipogenesis, altered DNA repair signaling, and enhanced antitumor or metabolic benefit, supporting continued interest in FASN-directed strategies for metabolic dysfunction–associated steatotic liver disease, liver cancer, and colorectal cancer.