title: Biomarkers of Morbid Obesity and Prediabetes by Metabolomic Profiling of Human Discordant Phenotypes.
abstract: Metabolomic studies aimed to dissect the connection between the development of type 2 diabetes and obesity are still scarce. In the present study, fasting serum from sixty-four adult individuals classified into four sex-matched groups by their BMI [non-obese versus morbid obese] and the increased risk of developing diabetes [prediabetic insulin resistant state versus non-prediabetic non-insulin resistant] was analyzed by LC- and FIA-ESI-MS/MS-driven metabolomic approaches. Altered levels of [lyso]glycerophospholipids was the most specific metabolic trait associated to morbid obesity, particularly lysophosphatidylcholines acylated with margaric, oleic and linoleic acids [lysoPC C17:0: R=-0.56, p=0.0003; lysoPC C18:1: R=-0.61, p=0.0001; lysoPC C18:2 R=-0.64, p<0.0001]. Several amino acids were biomarkers of risk of diabetes onset associated to obesity. For instance, glutamate significantly associated with fasting insulin [R=0.5, p=0.0019] and HOMA-IR [R=0.46, p=0.0072], while glycine showed negative associations [fasting insulin: R=-0.51, p=0.0017; HOMA-IR: R=-0.49, p=0.0033], and the branched chain amino acid valine associated to prediabetes and insulin resistance in a BMI-independent manner [fasting insulin: R=0.37, p=0.0479; HOMA-IR: R=0.37, p=0.0468]. Minority sphingolipids including specific [dihydro]ceramides and sphingomyelins also associated with the prediabetic insulin resistant state, hence deserving attention as potential targets for early diagnosis or therapeutic intervention.
authors.affiliation: Biomarkers & Nutrimetabolomic Lab, Nutrition & Food Science Dept, XaRTA, INSA, Campus Torribera, Pharmacy and Food Science Faculty, University of Barcelona, 08028, Spain; Biomedical Research Institute [IBIMA], Service of Endocrinology and Nutrition, Malaga Hospital Complex [Virgen de la Victoria], Campus de Teatinos s/n, Malaga, Spain. Electronic address: sara.tulipani@ub.edu.
authors.forename: Sara
authors.initials: S
authors.lastname: Tulipani
authors.affiliation: Biomarkers & Nutrimetabolomic Lab, Nutrition & Food Science Dept, XaRTA, INSA, Campus Torribera, Pharmacy and Food Science Faculty, University of Barcelona, 08028, Spain.
authors.forename: Magali
authors.initials: M
authors.lastname: Palau-Rodriguez
authors.affiliation: Statistics Department, Biology Faculty, University of Barcelona, 08028, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Miñarro Alonso
authors.affiliation: Biomedical Research Institute [IBIMA], Service of Endocrinology and Nutrition, Malaga Hospital Complex [Virgen de la Victoria], Campus de Teatinos s/n, Malaga, Spain; CIBER Fisiopatología de la Obesidad y Nutrición [CIBERobn], Instituto de Salud Carlos III [ISCIII], Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Cardona
authors.affiliation: Biomarkers & Nutrimetabolomic Lab, Nutrition & Food Science Dept, XaRTA, INSA, Campus Torribera, Pharmacy and Food Science Faculty, University of Barcelona, 08028, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Marco-Ramell
authors.affiliation: Water and Soil Quality Research Group, Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research [IDAEA-CSIC], Barcelona, Spain.
authors.forename: Bozo
authors.initials: B
authors.lastname: Zonja
authors.affiliation: Water and Soil Quality Research Group, Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research [IDAEA-CSIC], Barcelona, Spain.
authors.forename: Miren
authors.initials: M
authors.lastname: Lopez de Alda
authors.affiliation: Biomedical Research Institute [IBIMA], Service of Endocrinology and Nutrition, Malaga Hospital Complex [Virgen de la Victoria], Campus de Teatinos s/n, Malaga, Spain; CIBER Fisiopatología de la Obesidad y Nutrición [CIBERobn], Instituto de Salud Carlos III [ISCIII], Madrid, Spain.
authors.forename: Araceli
authors.initials: A
authors.lastname: Muñoz-Garach
authors.affiliation: Statistics Department, Biology Faculty, University of Barcelona, 08028, Spain; Statistics and Bioinformatics Unit Vall d'Hebron Institut de Recerca [VHIR], 08035, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sanchez-Pla
authors.affiliation: Biomedical Research Institute [IBIMA], Service of Endocrinology and Nutrition, Malaga Hospital Complex [Virgen de la Victoria], Campus de Teatinos s/n, Malaga, Spain; CIBER Fisiopatología de la Obesidad y Nutrición [CIBERobn], Instituto de Salud Carlos III [ISCIII], Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Tinahones
authors.affiliation: Biomarkers & Nutrimetabolomic Lab, Nutrition & Food Science Dept, XaRTA, INSA, Campus Torribera, Pharmacy and Food Science Faculty, University of Barcelona, 08028, Spain. Electronic address: candres@ub.edu.
authors.forename: Cristina
authors.initials: C
authors.lastname: Andres-Lacueva
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D009767:Obesity, Morbid / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D010641:Phenotype; D011236:Prediabetic State / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*
chemical_list: D015415:Biomarkers
keywords: mass spectrometry; metabolic markers; obesity; observational study; prediabetes