Lipogénesis

Lipogénesis, or lipogenesis, is the metabolic pathway by which acetyl-CoA is converted into fatty acids, primarily for storage as triglycerides. In humans, the liver and adipose tissue are the principal sites of de novo lipogenesis, which increases in the fed state after carbohydrate-rich meals.

The process begins with glucose-derived acetyl-CoA in the cytosol. Since acetyl-CoA cannot cross the mitochondrial membrane, citrate is exported to the cytosol and cleaved back to acetyl-CoA and oxaloacetate by ATP citrate lyase. Acetyl-CoA is carboxylated to malonyl-CoA by acetyl-CoA carboxylase, a key rate-limiting enzyme. Fatty acid synthase then iteratively elongates the growing fatty acid chain, ultimately producing palmitate (C16:0). Subsequent elongation and desaturation yield longer and unsaturated fatty acids. Reducing power for these reactions is provided predominantly by NADPH, generated by the pentose phosphate pathway, malic enzyme, and cytosolic isocitrate dehydrogenase. Glycerol-3-phosphate, derived from glycolysis, provides the glycerol backbone for triglyceride assembly.

Stored results and export: fatty acids are esterified to glycerol to form triglycerides, which are stored in adipose tissue or exported from the liver as very-low-density lipoprotein (VLDL).

Regulation and physiology: insulin stimulates lipogenesis by activating acetyl-CoA carboxylase and promoting citrate supply, while AMP-activated protein kinase inhibits ACC. Malonyl-CoA also inhibits fatty acid oxidation by reducing transport into mitochondria. Lipogenesis adapts to energy balance and hormonal signals; excessive lipogenesis is linked to hepatic steatosis and metabolic syndrome in certain conditions, whereas it declines during fasting.