Metabolomics-guided insights on bariatric surgery versus behavioral interventions for weight loss.

OBJECTIVE: To review the metabolomic studies carried out so far to identify metabolic markers associated with surgical and dietary treatments for weight loss in subjects with obesity. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: Thirty-two studies successfully met the eligibility criteria. The metabolic adaptations shared by surgical and dietary interventions mirrored a state of starvation ketoacidosis (increase of circulating ketone bodies), an increase of acylcarnitines and fatty acid ß-oxidation, a decrease of specific amino acids including branched-chain amino acids (BCAA) and (lyso)glycerophospholipids previously associated with obesity, and adipose tissue expansion. The metabolic footprint of bariatric procedures was specifically characterized by an increase of bile acid circulating pools and a decrease of ceramide levels, a greater perioperative decline in BCAA, and the rise of circulating serine and glycine, mirroring glycemic control and inflammation improvement. In one study, 3-hydroxybutyrate was particularly identified as an early metabolic marker of long-term prognosis after surgery and proposed to increase current prognostic modalities and contribute to personalized treatment. CONCLUSIONS: Metabolomics helped in deciphering the metabolic response to weight loss treatments. Moving from association to causation is the next challenge to move to a further level of clinical application.

Plasma metabolomic biomarkers of mixed nuts exposure inversely correlate with severity of metabolic syndrome.

SCOPE: To identify the most discriminant dietary biomarkers of nuts exposure in subjects with metabolic syndrome (MetS), and investigate the potential association between exposure and the severity of the MetS diagnostic traits. METHODS AND RESULTS: We applied the untargeted LC-ESI-qToF-MS-driven metabolomic workflow to explore the changes occurring in the plasma metabolome of MetS subjects following 12-wk intake of mixed nuts (30 g/d; nuts versus control groups). Urolithin A glucuronide was the most discriminative biomarker of nuts exposure, showing the highest predictive capacity (area under the ROC curve = 89.6% [80.8-98.4]) despite the interindividual variation expected for a host-microbial cometabolite. Furthermore, the detection of urolithin A glucuronide in plasma showed significant inverse correlation with basal abdominal adiposity (waist circumference: r = -0.550, p < 0.01; waist-hip ratio: r = -0.409, p < 0.05) and impaired glycemic control (fasting insulin: r = -0.414, p < 0.05; HOMA-IR: r = -0.417, p < 0.05). Significant changes in medium-chain dicarboxylic acids, recognized as alternative energy substrates that are particularly relevant in the case of glycemic control impairment, were also associated with nut consumption. CONCLUSION: Higher levels of utolithin A glucuronide are reported in subjects with less severe MetS traits, especially in females. We believe that this inverse correlation may be related with profile of gut microbial dysbiosis, recently associated to subjects with MetS.

New and vintage solutions to enhance the plasma metabolome coverage by LC-ESI-MS untargeted metabolomics: the not-so-simple process of method performance evaluation.

Although LC-MS untargeted metabolomics continues to expand into exiting research domains, methodological issues have not been solved yet by the definition of unbiased, standardized and globally accepted analytical protocols. In the present study, the response of the plasma metabolome coverage to specific methodological choices of the sample preparation (two SPE technologies, three sample-to-solvent dilution ratios) and the LC-ESI-MS data acquisition steps of the metabolomics workflow (four RP columns, four elution solvent combinations, two solvent quality grades, postcolumn modification of the mobile phase) was investigated in a pragmatic and decision tree-like performance evaluation strategy. Quality control samples, reference plasma and human plasma from a real nutrimetabolomic study were used for intermethod comparisons. Uni- and multivariate data analysis approaches were independently applied. The highest method performance was obtained by combining the plasma hybrid extraction with the highest solvent proportion during sample preparation, the use of a RP column compatible with 100% aqueous polar phase (Atlantis T3), and the ESI enhancement by using UHPLC-MS purity grade methanol as both organic phase and postcolumn modifier. Results led to the following considerations: submit plasma samples to hybrid extraction for removal of interfering components to minimize the major sample-dependent matrix effects; avoid solvent evaporation following sample extraction if loss in detection and peak shape distortion of early eluting metabolites are not noticed; opt for a RP column for superior retention of highly polar species when analysis fractionation is not feasible; use ultrahigh quality grade solvents and "vintage" analytical tricks such as postcolumn organic enrichment of the mobile phase to enhance ESI efficiency. The final proposed protocol offers an example of how novel and old-fashioned analytical solutions may fruitfully cohabit in untargeted metabolomics protocols.

Cocoa polyphenols and inflammatory markers of cardiovascular disease.

Epidemiological studies have demonstrated the beneficial effect of plant-derived food intake in reducing the risk of cardiovascular disease (CVD). The potential bioactivity of cocoa and its polyphenolic components in modulating cardiovascular health is now being studied worldwide and continues to grow at a rapid pace. In fact, the high polyphenol content of cocoa is of particular interest from the nutritional and pharmacological viewpoints. Cocoa polyphenols are shown to possess a range of cardiovascular-protective properties, and can play a meaningful role through modulating different inflammatory markers involved in atherosclerosis. Accumulated evidence on related anti-inflammatory effects of cocoa polyphenols is summarized in the present review.