Lipid synthesis

Lipid synthesis, specifically de novo lipogenesis (DNL), is a fundamental biological process involving the enzymatic conversion of non-lipid precursors like acetyl-CoA into fatty acids and cholesterol (StatPearls, 2023). This pathway is crucial for maintaining cellular membrane integrity, providing high-density energy storage, and producing essential signaling molecules. In various pathologies, including nonalcoholic steatohepatitis (NASH) and many types of cancer, lipid synthesis is significantly upregulated to facilitate rapid cell proliferation and energy demands (Nature Reviews Cancer, 2020). While 'lipid synthesis' refers to a broad metabolic pathway rather than a single molecular target, it serves as a therapeutic framework where specific enzymes such as Fatty acid synthase (FASN), Acetyl-CoA carboxylase (ACC), and HMG-CoA reductase (HMGCR) are targeted by drugs. For example, statins inhibit cholesterol synthesis to manage cardiovascular risk, while novel FASN inhibitors like denifanstat are being evaluated for their ability to reduce hepatic fat and inhibit tumor growth (PubMed, 2021). Therapeutic targeting of these pathways requires careful monitoring of biomarkers like hepatic fat fraction and serum triglycerides to ensure efficacy and avoid toxicities related to essential lipid depletion.

Other names

De novo lipogenesisFatty acid synthesisSterol synthesisLipogenesisLipid biosynthetic process

Inhibition of specific rate-limiting enzymes within the biosynthetic pathway, such as HMG-CoA reductase, Acetyl-CoA carboxylase (ACC), or Fatty acid synthase (FASN), to reduce the accumulation of fatty acids, cholesterol, or other lipid species.