Adipose Tissue Protein Glycoxidation is Associated with Weight-Loss Potential

Abstract

Objective: This study aimed to characterize the differences in protein oxidation biomarkers in adipose tissue (AT) as an indicator of AT metabolism and bariatric surgery weight-loss success.

Methods: A human model, in which sixty-five individuals with obesity underwent bariatric surgery, and a diet-induced obesity animal model, in which animals were treated for 2 months with normocaloric diets, were analyzed to determine the associations between AT protein oxidation and body weight loss. Protein oxidative biomarkers were determined by gas chromatography/mass spectrometry in AT from human volunteers before the surgery, as well as 2 months after a diet treatment in the animal model.

Results: The levels of carboxyethyl-lysine (CEL) and 2-succinocystein (2SC) in both visceral and subcutaneous AT before the surgery directly correlated with greater weight loss in both human and animal models. 2SC levels in subcutaneous AT greater than 4.7 × 106 μmol/mol lysine (95% CI: 3.4 × 106 to 6.0 × 106 ) may predict greater weight loss after bariatric surgery (receiver operating characteristic curve area = 0.8222; P = 0.0047). Additionally, it was observed that individuals with diabetes presented lower levels of CEL and 2SC in subcutaneous AT (P = 0.0266 and P = 0.0316, respectively) compared with individuals without diabetes.

Conclusions: CEL and 2SC in AT are useful biomarkers of AT metabolism and predict the individual's ability to reduce body weight after bariatric surgery.

© 2019 The Authors. Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).

Figures

Figure 1

Adipose tissue protein oxidative damage markers. (A) Correlation table of the values of protein oxidative biomarkers in SAT and VAT. Color of circles indicates the Spearman correlation coefficient, such that the red color describes a direct proportion correlation while the blue color inverse proportion. Size of circle denotes the significance of the correlation. The larger the size, the closer the P values are to 0. (B‐E) Correlation between EWL12 and the preoperative values of CEL and 2SC in SAT and VAT. B slope = 10.4 ± 3.2 (r2 = 0.2212, P = 0.0025, and q = 0.0048); C slope = 6.8 ± 2.4 (r2 = 0.1775, P = 0.0084, and q = 0.0149); D slope = 85,094 ± 23,256 (r2 = 0.2711, P = 0.0008, and q = 0.0012); and E slope = 35,376 ± 17,575 (r2 = 0.1037, P = 0.0495, and q = 0.0495). Direct proportional correlation was observed between the levels of CEL and 2SC in SAT and CEL in VAT with EWL. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 2

Differences in CEL and 2SC in SAT and VAT from participants with or without diabetes mellitus (DM) and ROC analysis for the use of SAT's 2SC levels as a predictor of weight loss. (A,B) Volunteers without DM presented higher values of CEL and 2SC in SAT compared with the participants with DM (P = 0.0266 and P = 0.0316, respectively). (C) ROC curve for SAT's levels of 2SC as a predictor of EWL12. (D) 2SC in SAT at lower and higher 95% CIs of volunteers’ EWL12. “*” denotes statistical differences between the selected parameters. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 3

Correlation between CEL content in mice adipose tissue and postdietary treatment outcomes. (A‐C) Inverse correlation was observed between CEL content and both final body weight and the area under the curve after a subcutaneous glucose tolerance and insulin test (slope −0.054 ± 0.017 [r2 = 0.1651] for body weight; slope −31.6 ± 15.5 [r2 = 0.2702, P = 0.0474, q = 0.0686] and slope −18.13 ± 8.18 [r2 = 0.0928, P = 0.0314, q = 0.0419] for the area under the curve for glucose and insulin tests, respectively). (D) Correlation and cluster analysis between different biomarkers of protein oxidative damage (2SC, GSA, CEL, CML, and MDAL) in adipose tissue, muscle, and liver. Red squares denote positive correlations and blue squares negative correlations. Letters beside initials of biomarkers correspond to the following: A, adipose tissue; L, liver; M, muscle. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 4

Proposed mechanism of the observed effects. Prior to the surgery, participants underwent a weight‐reduction plan. Patients with metabolic flexibility and/or insulin sensitivity will have the ability to uptake glucose and metabolize it. Increase in glycolytic pathways may induce higher levels of fumarate, which is highly reactive to protein‐cysteine, and 2SC adducts may be formed. As a side effect of the increase in the glycolytic pathways, methylglyoxal may be formed from glyceraldehyde‐3‐P. Because of the reactivity of methylglyoxal, CEL adducts may be formed. Patients without metabolic flexibility and/or insulin sensitivity will have a reduced flux in the glycolytic pathways, which in turn will show lower levels of 2SC and CEL adducts. [Colour figure can be viewed at wileyonlinelibrary.com]