Circulating Unsaturated Fatty Acids Delineate the Metabolic Status of Obese Individuals

BACKGROUND: Obesity is not a homogeneous condition across individuals since about 25–40% of obese individuals can maintain healthy status with no apparent signs of metabolic complications. The simple anthropometric measure of body mass index does not always reflect the biological effects of excessive body fat on health, thus additional molecular characterizations of obese phenotypes are needed to assess the risk of developing subsequent metabolic conditions at an individual level. METHODS: To better understand the associations of free fatty acids (FFAs) with metabolic phenotypes of obesity, we applied a targeted metabolomics approach to measure 40 serum FFAs from 452 individuals who participated in four independent studies, using an ultra-performance liquid chromatograph coupled to a Xevo G2 quadruple time-of-flight mass spectrometer. FINDINGS: FFA levels were significantly elevated in overweight/obese subjects with diabetes compared to their healthy counterparts. We identified a group of unsaturated fatty acids (UFAs) that are closely correlated with metabolic status in two groups of obese individuals who underwent weight loss intervention and can predict the recurrence of diabetes at two years after metabolic surgery. Two UFAs, dihomo-gamma-linolenic acid and palmitoleic acid, were also able to predict the future development of metabolic syndrome (MS) in a group of obese subjects. INTERPRETATION: These findings underscore the potential role of UFAs in the MS pathogenesis and also as important markers in predicting the risk of developing diabetes in obese individuals or diabetes remission after a metabolic surgery.