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. Author manuscript; available in PMC: 2021 May 19.
Published in final edited form as: Curr Cardiol Rep. 2020 Oct 10;22(12):174. doi: 10.1007/s11886-020-01422-x

Table 2.

Overview of metabolomic studies of obesity

Study population and sample size Platform Key Significant Metabolites Other Outcomes
Obesity/BMI
 STEDMAN [104]
  - 74 Obese
  - 67 Lean		 Targeted MS/MS

  • BCAAs and aromatic AAs

  • C3 and C5 acylcarnitines

  • Glycine (−)

 Insulin resistance
 European Diogenes Study [107]
  - 634 Overweight/Obese		 NMR

  • BCAAs

  • Triglycerides

  • Lactate

  • Glycine (−)

 Hepatic insulin resistance and Skeletal muscle insulin sensitivity
 MURDOCK [119]
  - 610 Overweight
  - 852 Obese
  - 410 Lean		 MS/MS

  • BCAAs

 Metabolic health
  - 43 Normal Weight Obesity [120] (BMI <25 and body fat > 30% for women and > 25% for men)
  - 110 Overweight/Obesity
  - 26 Lean		 LC ESI-MS

  • BCAAs and aromatic AAs

  • Linoleic acid

 Body Composition Subtypes
 SAFHS [123]
  - 1431 Adults		 LC ESI-MS/MS

  • Cholesterol esters

  • Triacylgylcerols

  • Ceramide

  • Lysophospholipids (−)

 Anthropometric and biochemical measurements
 Western Australian Pregnancy Cohort [124]
  - 1176 Women		 MS

  • Sphingomyelins

  • Diacylphosphatidylcholines

  • Lysophosphatidylcholines (−)

 Waist Circumference
Insulin resistance
  - 34 Metabolically Healthy Obese [125]
  - 38 Metabolically Unhealthy Obese		 LC/MS & GC/MS

  • Glycerophosphocholine (−)

  • Glycerol 1-phosphate (−)

 Metabolic Health
  - 107 Metabolically Healthy Obese [126]
  - 100 Metabolically Unhealthy Obese
  - 78 Normal Weight Metabolically Healthy		 LC-MS/MS

  • BCAAs

  • Diacylphosphatidylcholines

  • LCAC (−)

  • Acyl-lysophosphatidylcholines (−)

  • Alkyl-lysophosphatidylcholine (−)

  • Acyl-alkyl-phosphatidylcholine (−)

 Metabolic Health
Cardiometabolic Biomarkers
  - 10 Obese without T2DM [127]
  - 9 Obese T2DM
  - 11 Lean		 LC/MS

  • Lysophosphatidylcholines (−)
 Boston Puerto Rican Health Study [128]
  - 781 Adults		 LC/MS

  • 148 metabolites correlated metabolites with BMI

  • 86 metabolites correlated with SSB intake

  • Phosphatidylcholine and lysophospholipid pathways linked to SSB intake and obesity

 Sugar-sweetened beverage (SSB) consumption and obesity risk
  - 14 Obese without T2DM [129]
  - 10 T2DM
  - 12 Lean		 MS/MS

  • LCACs

  • Free Carnitines

 Glycemic control
Acylcarnitines levels following insulin infusion
  - 6 Obese [130]
  - 6 Lean
Before and after 5-day high-fat diet		 MS/MS

  • Plasma SCACs

  • Skeletal muscle AAs (−)

  • Skeletal muscle MCACs

 Plasma and Skeletal Muscle metabolomics
 Six independent cohorts [131]
  - 739 Adults		 Targeted MS

  • BCAAs and aromatic AAs

  • MCACs and LCACs

  • Glycine (−)

 Age
  - 35 Men [132]
  - 47 Women		 NMR

  • Serine (−)

  • Glycine (−)

 Metabolic health
Activity Energy Expenditure
Sedentary Time and Activity Reporting Questionnaire
 TwinsUK Registry [133]
  - 1,969 Twins		 UPLC-MS/MS

  • Nucleotides, including urate

  • Peptides

 Cardiovascular events
  - 85 Obese [134]
  - 42 Non-Obese		 LC ESI-MS/MS

  • Kynurenine/Tryptophan ratio

  • Serotonin (5-HT) and indoles (−)

 Interleukin-6
C-reactive protein
Gestational Obesity
 HAPO Study [135••]
  - 1600 Pregnant Women		 Targeted MS/MS

  • BCAAs and aromatic AAs

  • Glycine (−)

  • Triglycerides

  • NEFA

  • MCACs

  • LCACs

 Insulin resistance
 HAPO Study [136]
  - 1412 Pregnant Women		 Targeted MS/MS and Non-targeted GC-MS

  • Variants in glucokinase regulatory protein gene associated with palmitoleic acid

 GWAS
Insulin resistance
Pediatric Obesity
 - 80 Obese Children [137]
  - 40 Normal Weight Children		 LC-MS/MS

  • Glutamine (−)

  • Methionine (−)

  • Proline (−)

  • Phosphatidylcholines (−)

  • LCACs

 Pubertal stage
  - 2191 Healthy Participants (age 3 months to 18 years) [138] LC-MS/MS

  • BCAAs and aromatic AAs

  • C3 carnitine

  • Citrulline (−)

  • Glycine (−)

 Pubertal stage
  - 524 Adolescents (age ~ 13 years) [139] Non-targeted LC-MS

  • BCAAs

  • Diacylgylcerols

  • Steroid hormones

  • LCACs

 Metabolic health
 Systematic Review [140]
  - 10 Studies
  - 2,673 Participants		 Varied

  • BCAAs and aromatic AAs

  • Lipid metabolism

 Insulin resistance
Behavioral Weight Loss Intervention
 Weight Loss Maintenance Study [141]
  - 500 Participants with ≥ 4kg Weight Loss
  - 22 Participant Independent Validation Cohort		 Targeted MS/MS

  • BCAAs and associated catabolites

 Change in insulin resistance independent of amount of weight lost
Surgical Weight Loss Intervention
 - 16 Gastric Bypass [142]
 - 17 Dietary Intervention
Matched 10 kg weight loss		 MS/MS

  • BCAAs, total AAs and C3 and C5 acylcarnitines derived from BCAA oxidation decreased after gastric bypass but not dietary intervention and correlate with insulin resistance.

 Insulin resistance
 - 10 Gastric Bypass [143]
 - 10 Laparoscopic adjustable gastric banding
~20% weight loss		 MS/MS

  • BCAAs, C3 and C5 acylcarnitines decreased similarly between surgical groups and correlate with insulin resistance

 Insulin resistance

Except where specified by (−), higher metabolites levels are associated with increased BMI or other outcomes noted in the table. In studies where examined, metabolic health is defined as a combination of one or more abnormal measures of waist circumference, blood glucose, hypertension, dyslipidemia, and insulin resistance

Abbreviations: MS, mass spectrometry; MS/MS, tandem mass spectrometry; LC, liquid chromatography; GC, gas chromatography; LC ESI-MS, liquid chromatography-electrospray ionization-mass spectrometry; UPLC-MS/MS, ultra-high-performance liquid chromatography-tandem mass spectrometry; NMR, nuclear-magnetic-resonance; BCAA, branched-chain amino acid; AA, amino acids; NEFA, non-esterified fatty acids; SCACs, short-chain acylcarnitines; MCACs, medium-chain acylcarnitines; LCACs, long-chain acylcarnitines