Non-esterified fatty acid (NEFA) (NEFA)

Serum fatty acids, primarily measured as the non-esterified fatty acid (NEFA) or free fatty acid (FFA) fraction, are essential circulating lipids that function both as major oxidative energy substrates and potent signaling molecules [4, 8]. They are primarily released from adipose tissue via lipolysis, transported in the bloodstream bound to albumin, and taken up by peripheral tissues such as the heart and skeletal muscle for ATP production through beta-oxidation [1, 8]. Beyond their metabolic role, serum fatty acids serve as endogenous ligands for specific G-protein coupled receptors (e.g., GPR40, GPR120) and nuclear receptors such as Peroxisome Proliferator-Activated Receptors (PPARs), thereby regulating systemic glucose homeostasis, lipid metabolism, and immune responses [5, 9]. Chronically elevated levels of serum fatty acids are a key driver in the pathogenesis of metabolic syndrome, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD), primarily by inducing systemic insulin resistance and lipotoxicity [13, 16]. They also contribute to cardiovascular disease progression and certain cancers by promoting chronic inflammation and providing metabolic precursors for tumor growth [9, 11, 17]. Pharmacological management of serum fatty acids focuses on agents like niacin and insulin to inhibit adipose lipolysis, or fibrates and thiazolidinediones to enhance their oxidation and redistribution into storage, thereby reducing their harmful systemic effects [9, 13].

Other names

Free fatty acidFFASerum fatty acidPlasma fatty acidCirculating fatty acidNon-esterified fatty acid

Drugs modulate serum fatty acid levels by inhibiting lipolysis in adipose tissue (e.g., niacin, insulin), activating PPAR-alpha to enhance hepatic oxidation (e.g., fibrates), promoting the sequestration of lipids into subcutaneous fat (e.g., thiazolidinediones), or reducing dietary fat absorption (e.g., orlistat) [9, 11, 13, 16].