Lipid metabolism comprises the synthesis, modification, transport and breakdown of fats that are essential for energy supply, membrane structure and signaling. A central aspect is the balance between lipid uptake and endogenous production. Cells import fatty acids and cholesterol from lipoproteins while also synthesizing them de novo from acetyl CoA. These processes are tightly regulated by nutrient status, hormones such as insulin and glucagon, and transcription factors including SREBP and PPARs.

Fatty acid oxidation in mitochondria converts long chain fatty acids into acetyl CoA via beta oxidation, feeding the citric acid cycle and oxidative phosphorylation to generate ATP. In fasting or carbohydrate restriction, excess acetyl CoA is diverted in the liver to form ketone bodies, which provide fuel for brain and muscle. Conversely, in the fed state, acetyl CoA supports fatty acid and triglyceride synthesis in liver and adipose tissue, promoted by high insulin and citrate levels.

Cholesterol metabolism is intertwined with fatty acid pathways. Cholesterol is synthesized from acetyl CoA through the mevalonate pathway, incorporated into membranes, converted to bile acids or packaged into lipoproteins. Feedback mechanisms adjust synthesis to dietary intake and cellular demand.

Disruptions in lipid metabolism underlie major diseases. Obesity, insulin resistance, nonalcoholic fatty liver disease and atherosclerosis arise from excess lipid accumulation, altered lipoprotein profiles and chronic inflammation. Cancer cells frequently reprogram lipid metabolism to support rapid growth, membrane production and stress resistance, increasing de novo fatty acid synthesis and uptake. Understanding the regulatory networks that coordinate lipid synthesis, storage, oxidation and transport is guiding development of therapies that target key enzymes and signaling pathways in metabolic and cardiovascular disorders and in oncology.