De Novo Lipogenesis

De novo lipogenesis (DNL) is the metabolic process by which cells synthesize new fatty acids from acetyl-CoA rather than obtaining those fatty acids directly from dietary or stored fat. Acetyl-CoA can be generated from several metabolic sources, including carbohydrate metabolism. In humans, DNL occurs prominently in the liver and also in adipose tissue .^1,2

During DNL, acetyl-CoA is first converted to malonyl-CoA by the enzyme acetyl-CoA carboxylase. Fatty acid synthase then uses acetyl-CoA and repeated malonyl-CoA units to build a fatty-acid chain, using NADPH as reducing power. A principal product is the 16-carbon saturated fatty acid palmitate, which can subsequently be elongated, desaturated, or incorporated into more complex lipids .^1,2

Carbohydrate can provide carbon for DNL after glucose or fructose is metabolized through pathways that ultimately generate cytosolic acetyl-CoA. The pathway is regulated by metabolic and hormonal conditions, including carbohydrate availability and insulin signaling. DNL therefore links carbohydrate metabolism with fatty-acid synthesis, but dietary carbohydrate is not necessarily converted into fat through this pathway .^1,2

De novo lipogenesis is distinct from triglyceride synthesis. DNL specifically creates new fatty-acid chains, whereas triglyceride synthesis attaches fatty acids to a glycerol backbone. Those fatty acids may have been synthesized through DNL, obtained from dietary fat, or released from existing lipid stores .¹