Thematic review series: Patient-Oriented Research. Free fatty acid metabolism in human obesity

Adipose tissue lipolysis provides circulating FFAs to meet the body’s lipid fuel demands. FFA release is well regulated in normal-weight individuals; however, in upper-body obesity, excess lipolysis is commonly seen. This abnormality is considered a cause for at least some of the metabolic defects (dyslipidemia, insulin resistance) associated with upper-body obesity. “Normal” lipolysis is sex-specific and largely determined by the individual’s resting metabolic rate. Women have greater FFA release rates than men without higher FFA concentrations or greater fatty acid oxidation, indicating that they have greater nonoxidative FFA disposal, although the processes and tissues involved in this phenomenon are unknown. Therefore, women have the advantage of having greater FFA availability without exposing their tissues to higher and potentially harmful FFA concentrations. Upper-body fat is more lipolytically active than lower-body fat in both women and men. FFA released by the visceral fat depot contributes only a small percentage of systemic FFA delivery. Upper-body subcutaneous fat is the dominant contributor to circulating FFAs and the source of the excess FFA release in upper-body obesity. We believe that abnormalities in subcutaneous lipolysis could be more important than those in visceral lipolysis as a cause of peripheral insulin resistance. Understanding the regulation of FFA availability will help to discover new approaches to treat FFA-induced abnormalities in obesity.