Circulating Unsaturated Fatty Acids Delineate the Metabolic Status of Obese Individuals

• Four independent studies were applied to examine the association of free fatty acids with metabolic status of obesity.
• Our data supported an important role for unsaturated fatty acids in the pathogenesis of metabolic syndrome.
• Two unsaturated fatty acids were predictive of future diabetes risk and diabetes remission after metabolic surgery.About 25–40% of obese individuals, defined by the body mass index, are metabolically healthy. Because obesity is a risk factor for developing type 2 diabetes, it is important to monitor obese individuals for changes in metabolic status. Simpler means of assessing the efficacy of surgical or dietary interventions are also desirable. We examined blood fatty acid levels in patients to locate potential biomarkers that would signify either greater risk of diabetes acquisition or effectiveness of diabetes treatment. Two unsaturated fatty acids, dihomo-gamma-linolenic acid and palmitoleic acid, were shown to predict acquisition of diabetes and also evaluate diabetes remission post-metabolic surgery.

BackgroundObesity 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.MethodsTo 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.FindingsFFA 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.InterpretationThese 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.