title: Circulating Unsaturated Fatty Acids Delineate the Metabolic Status of Obese Individuals.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China ; University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China ; University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Linjing
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai 200233, China.
authors.forename: Haoyong
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai 200233, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Ma
authors.affiliation: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China ; Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai 200233, China.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Bao
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Rajani
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Lenora W M
authors.initials: LW
authors.lastname: Loo
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Yurii B
authors.initials: YB
authors.lastname: Shvetsov
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
authors.affiliation: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Tianlu
authors.initials: T
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China ; Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai 200233, China.
authors.forename: Congrong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China ; Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai 200233, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Hu
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Mingming
authors.initials: M
authors.lastname: Su
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Xie
authors.affiliation: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhao
authors.affiliation: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China ; University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China ; Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai 200233, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
mesh_terms: D000328:Adult; D015415:Biomarkers; D002851:Chromatography, High Pressure Liquid; D016000:Cluster Analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D005231:Fatty Acids, Unsaturated / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000209:etiology; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000178:diet therapy / Q000378:metabolism*; D016017:Odds Ratio; D050177:Overweight / Q000097:blood / Q000150:complications; D010641:Phenotype; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D005231:Fatty Acids, Unsaturated
keywords: AA, arachidonic acid; BMI, body mass index; CVD, cardiovascular disease; DAG, diacylglycerol; DBP, diastolic blood pressure; DGLA, dihomo-gamma-linolenic acid; DNL, de novo lipogenesis; FATPs, fatty acid transport proteins; FFA, free fatty acids; Free fatty acids; GLA, γ-linolenic acid; HA, heptadecanoic acid; HDL, high-density lipoprotein; HO, metabolically healthy obese; HbA1c, glycated hemoglobin; Insulin resistance; LA, linoleic acid; LDL, low-density lipoprotein; MS, metabolic syndrome; MUFA, monounsaturated acid; Metabolic syndrome; NAFLD, nonalcoholic fatty liver disease; NW, normal weight; OGTT, oral glucose tolerance test; OPLS-DA, orthogonal partial least square discriminant analysis; Obesity; PA, palmitoleic acid; PUFA, polyunsaturated fatty acid; RSD, relative standard deviation; SBP, systolic blood pressure; SCD, stearoyl-CoA desaturase; SFA, saturated fatty acid; SHDS, the Shanghai Diabetes Study; SHOS, the Shanghai Obesity Study; T2D, type 2 diabetes; TC, total cholesterol; TG, triglycerides; Type 2 diabetes; UFA, unsaturated fatty acid; UO, metabolically unhealthy obese; Unsaturated fatty acids; VLCD, very low carbohydrate diet