Free-amino acid metabolic profiling of visceral adipose tissue from obese subjects
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ORIGINAL ARTICLE
Free‑amino acid metabolic profiling of visceral adipose tissue from obese subjects M. C. Piro1 · M. Tesauro2 · A. M. Lena1 · P. Gentileschi3 · G. Sica3 · G. Rodia2 · M. Annicchiarico‑Petruzzelli4 · V. Rovella2 · C. Cardillo5 · G. Melino1,6 · E. Candi1,4 · N. Di Daniele2 Received: 14 October 2019 / Accepted: 26 July 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract Interest in adipose tissue pathophysiology and biochemistry have expanded considerably in the past two decades due to the ever increasing and alarming rates of global obesity and its critical outcome defined as metabolic syndrome (MS). This obesity-linked systemic dysfunction generates high risk factors of developing perilous diseases like type 2 diabetes, cardiovascular disease or cancer. Amino acids could play a crucial role in the pathophysiology of the MS onset. Focus of this study was to fully characterize amino acids metabolome modulations in visceral adipose tissues (VAT) from three adult cohorts: (i) obese patients (BMI 43–48) with metabolic syndrome (PO), (ii) obese subjects metabolically well (O), and (iii) non obese individuals (H). 128 metabolites identified as 20 protein amino acids, 85 related compounds and 13 dipeptides were measured by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) and gas chromatography-/ mass spectrometry GC/MS, in visceral fat samples from a total of 53 patients. Our analysis indicates a probable enhanced BCAA (leucine, isoleucine, valine) degradation in both VAT from O and PO subjects, while levels of their oxidation products are increased. Also PO and O VAT samples were characterized by: elevated levels of kynurenine, a catabolic product of tryptophan and precursor of diabetogenic substances, a significant increase of cysteine sulfinic acid levels, a decrease of 1-methylhistidine, and an up regulating trend of 3-methylhistidine levels. We hope this profiling can aid in novel clinical strategies development against the progression from obesity to metabolic syndrome. Keywords Obesity · Metabolomics · Body mass index · Metabolic syndrome · Branched chain amino acids · Histidine · Tryptophan · Adipose tissue Abbreviations BMI Body mass index HDL High-density lipoprotein GC/MS Gas chromatography/mass spectrometry LC/MS/MS Liquid chromatography/mass spectrometry RF Random forest analysis Handling editor: K. Barnouin. M. C. Piro and M. Tesauro are co-first authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00726-020-02877-6) contains supplementary material, which is available to authorized users. * E. Candi [email protected] * N. Di Daniele [email protected] Extended author information available on the last page of the article
H Healthy O Obese PO Pathological obese BKCDH Branched-chain alpha-keto acid dehydrogenase complex IR Insulin resistant TCA Tricarboxylic acid cycle BCAA Branched chain amino acids MS Metabolic syndrome KYN Kynurenine KP
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