NEFA

Non-esterified fatty acids (NEFA), also called free fatty acids, are fatty acids circulating in the blood not bound to glycerol backbones as triglycerides or other complex lipids. In humans, most NEFA are bound loosely to albumin, which facilitates their transport to tissues where they can be oxidized for energy.

NEFA originate mainly from adipose tissue through lipolysis, a process activated by catecholamines during fasting or exercise and inhibited by insulin. The hydrolysis is initiated by adipose triglyceride lipase (ATGL) and continued by hormone-sensitive lipase (HSL), with additional contributions from other lipases. Plasma NEFA levels rise when lipolysis increases and insulin action decreases, and fall after meals when insulin suppresses lipolysis.

In target tissues, NEFA are taken up and converted to acyl-CoA, then transported into mitochondria by carnitine palmitoyltransferase I (CPT1) for beta-oxidation and ATP production. Beyond energy supply, NEFA also act as signaling molecules that influence metabolic pathways and gene expression.

Clinically, plasma NEFA concentrations reflect the rate of lipolysis and metabolic state. Persistently elevated NEFA levels are associated with insulin resistance, obesity, type 2 diabetes, and nonalcoholic fatty liver disease, while lower levels indicate greater insulin action. Measurements are performed with enzymatic or colorimetric assays and are typically reported in mmol/L or μmol/L, with fasting values varying by assay and physiological state.