Individual fatty acids, free fatty acids (FFA), or the non-esterified fatty acids (NEFA), circulate primarily in association with albumin. They are an important metabolic fuel. Non-esterified fatty acids (NEFA) are the major component of triglycerides, which consist of three fatty acids linked to a glycerol backbone. Hydrolysis of triglycerides in adipose tissue by hormone sensitive lipase liberates NEFAs and glycerol. Low concentrations of NEFAs are normally found in blood. Increased concentrations indicate breakdown of fat (lipolysis), which occurs in response to increased energy demand. NEFAs are considered a biomarker of negative energy balance, where the supply of glucose is insufficient to meet energy needs.

Fatty acids play a central role in providing energy to tissues, particularly during fasting. The liver, kidneys, myocardium, and skeletal muscles, but not the brain. The major storage form of fatty acids is in triglycerides (large amounts are also esterified to cholesterol or in phospholipids), and the enzymes lipoprotein lipase and hepatic lipase hydrolyze the triglycerides to fatty acids and glycerol, thereby releasing them as energy sources for the various tissues. FFA that have been released from triglyceride by the actions of lipoprotein lipase and hepatic lipase are elevated in blood of subjects with central obesity, insulin resistance and type II diabetes.