Plasma Free Fatty Acid Concentration as a Modifiable Risk Factor for Metabolic Disease

Plasma free fatty acid (FFA) concentration is elevated in obesity, insulin resistance (IR), non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), and related comorbidities such as cardiovascular disease (CVD). Furthermore, experimentally manipulating plasma FFA in the laboratory setting modulates metabolic markers of these disease processes. In this article, evidence is presented indicating that plasma FFA is a disease risk factor. Elevations of plasma FFA can promote ectopic lipid deposition, IR, as well as vascular and cardiac dysfunction. Typically, elevated plasma FFA results from accelerated adipose tissue lipolysis, caused by a high adipose tissue mass, adrenal hormones, or other physiological stressors. Reducing an individual's postabsorptive and postprandial plasma FFA concentration is expected to improve health. Lifestyle change could provide a significant opportunity for plasma FFA reduction. Various factors can impact plasma FFA concentration, such as chronic restriction of dietary energy intake and weight loss, as well as exercise, sleep quality and quantity, and cigarette smoking. In this review, consideration is given to multiple factors which lead to plasma FFA elevation and subsequent disruption of metabolic health. From considering a variety of medical conditions and lifestyle factors, it becomes clear that plasma FFA concentration is a modifiable risk factor for metabolic disease.