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Part of the equipment employed in this work has been funded by Generalitat Valenciana and co-financed with ERDF funds (OP ERDF of Comunitat Valenciana 2014-2020). J.M.-P. is funded by the Carlos III Health Institute (Madrid, Spain) through a Miguel Servet programme (CP18/00009). In addition, this work was supported by the Carlos III Health Institute and the European Regional Development Fund (PI16/02064, PI15/01934 and PI18/01022), and by CIBEROBN.

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Combining metabolic profiling of plasma and faeces as a fingerprint of insulin resistance in obesity

Publicat a:Clinical Nutrition. 39 (7): 2292-2300 - 2020-01-01 39(7), DOI: 10.1016/j.clnu.2019.10.022

Autors: Palomino-Schatzlein, M; Mayneris-Perxachs, J; Caballano-Infantes, E; Rodriguez, MA; Palomo-Buitrago, ME; Xiao, XP; Mares, R; Ricart, W; Simo, R; Herance, JR; Fernandez-Real, JM

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Background & aims: Insulin resistance (IR) is one of the main risk factor for type 2 diabetes mellitus (T2DM). Nevertheless, its underlying pathophysiology is not completely established because IR is triggered by a complex interconnection of numerous factors impairing metabolism, promoting metabolome changes. Methods: We used a metabolomics approach to identify plasma and faecal metabolites related to IR and obesity. We explored a cohort of 44 subjects at baseline, with 30 of them followed two years thereafter in a longitudinal study after an hypocaloric diet in the obese subjects. Results: In all individuals as a whole, 11 plasma metabolites positively associated with BMI (acetoacetate, creatinine, glycerol, glycerol of lipids, VLDL, fatty esters, myo-inositol, phenylalanine, threonine, tyrosine and valine) and one negatively (phosphocholine), with similar associations at baseline and follow-up. Four of these metabolites (myo-inositol, valine, acetoacetate and phosphocholine) remained significant within obese and non-obese groups. Thirteen faecal metabolites positively associated with BMI at baseline and one negatively (glutamine). However, these correlations did not remain significant at follow-up. The correlations were not always consistent at baseline and at follow-up and the metabolites that showed significant correlations were different for the obese group compared with the control group. The percent change in plasma Delta ethanolamine, Delta glucose, Delta uracil and Delta hypoxanthine were positively associated with Delta BMI. The percent change in plasma Delta phosphocholine and of faecal Delta hydroxyphenylacetate, and Delta 2-hydroxyphenylacetate were associated with Delta HOMA-IR in those patients that lost weight. Faecal branched chain amino acids (BCAAs) in faeces were associated with IR, following a similar pattern to that described for plasma BCAAs. Choline derivates had an opposite behaviour. Conclusions: The integration of plasma and faecal metabolites represents a valuable fingerprint that could help in the identification of patients at risk for IR and in the design of novel therapeutic strategies to prevent IR and the development of overt T2DM in the context of obesity. The results are coherent with diet having a much greater impact on faecal metabolomic profile than on plasma metabolome. (C) 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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