Lipogenese

Lipogenese, or lipogenesis, is the metabolic process by which acetyl-CoA is converted into fatty acids and then into glycerides for energy storage. In humans, the major sites are the liver and adipose tissue, where fatty acids are synthesized and triglycerides stored or exported as part of lipoproteins such as VLDL.

The process begins with cytosolic acetyl-CoA, produced from citrate exported from mitochondria and cleaved by ATP-citrate lyase. Acetyl-CoA carboxylase adds a carboxyl group to form malonyl-CoA, the committed step in fatty acid synthesis. Fatty acid synthase then catalyzes cycles that elongate the growing chain, predominantly yielding palmitate (C16:0). NADPH, supplied by the pentose phosphate pathway and the malic enzyme, provides reducing equivalents for synthesis. The resulting fatty acids are incorporated into glycerol backbones to form triglycerides, which can be stored in adipose tissue or exported as part of lipoproteins.

Regulation of lipogenesis is tightly controlled by hormonal and energy signals. Insulin promotes lipogenesis by increasing the activity and expression of lipogenic enzymes, while glucagon and adrenaline inhibit the process through signaling pathways that activate AMPK and reduce lipogenic gene expression. Citrate not only supplies acetyl-CoA but also activates acetyl-CoA carboxylase, whereas malonyl-CoA inhibits carnitine palmitoyltransferase I, linking lipid synthesis with reduced fatty acid oxidation. Transcription factors such as SREBP-1c and ChREBP respond to glucose and insulin to upregulate lipogenic genes.

Physiologically, lipogenesis supports energy storage in adipose tissue and contributes to hepatic lipid handling. Clinically, dysregulated lipogenesis is associated with metabolic conditions like obesity and non-alcoholic fatty liver disease, while reduced lipogenesis can occur in lipodystrophy or certain enzymatic defects. Lipogenesis is balanced by lipolysis and fatty acid oxidation to regulate whole-body energy homeostasis.