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Volatile organic compounds in obesity mouse models

Obesity is a worldwide epidemic linked to a number of co-morbidities, such as diabetes, cardiovascular disease, dyslipidemia and certain types of cancers. Easily accessible biomarkers are central to the assessment of individual risks of patients suffering from such pathologies and developing personalized medicine approaches for prevention and treatment.

A variety of normal and disease associated metabolic reactions produce small volatile organic compounds (VOCs), which can be detected in body fluids but also non-invasively in exhaled breath. Over the past decade, advances in the methodology made it possible to determine VOCs online in a concentration range of ppm to ppt and leading to studies that attempted to link VOC signatures to various pathologies. However, prerequisites for broader clinical application are (1) clear identification of the molecules that are exhaled as VOCs and (2) a better understanding of the considerable inter- and intra-individual variation in VOCs found in breath even in healthy humans.

The aim of the study conducted in the Energy Metabolism Laboratory in the GMC led by Martin Kistler and Jan Rozman was to characterize alterations in exhaled VOCs in a diet-induced (HFD) and a mono-genetic obese (melanocortin 4 receptor nonsense knock-in, MC4R-ki) mouse model and to evaluate whether a symptomatic pattern of VOCs related to obesity can be determined. In addition, the scientists were interested in individual changes specific for the volatilome of the two obese models showing distinct metabolic deregulations.

The analysis of the VOCs in both obesity models showed an overlap of eight peaks. These peaks were pk33B (methanol), pk50 (unassigned), pk61 (acetic acid), pk62 ((methylthio) methanethiol, MTMT), pk63 (CO2, dimethyl sulfide (DMS)), pk65B (CO2, DMS isotopes), pk81B (unassigned) and pk117B (unassigned). The scientists then generated a partial correlation network of the volatile metabolites. Thus, additional information on the chemical and metabolic origins of several volatiles could be obtained. HFD-induced obese mice showed for example an elevation in the ketone body acetone and acrolein, a marker of lipid peroxidation, and several unidentified volatiles. In MC4R-ki mice the pheromone MTMT was found to be reduced, linking metabolic dysfunction and reproduction. The results of this study also highlight that volatile metabolites derive from both mouse metabolism but also from gut microbiome metabolism that very likely interact especially in disease states.

In conclusion, the study shows that signatures of volatile metabolites can be instrumental in identifying and monitoring metabolic disease states. Therefore, breath gas analysis potentially offers a good possibility to non-invasively assess metabolic alterations for personalized diagnosis.

Martin Kistler, Andreea Muntean, Wilfried Szymczak, Nadine Rink, Helmut Fuchs,
Valerie Gailus-Durner, Wolfgang Wurst, Christoph Hoeschen, Martin Klingenspor,
Martin Hrabe de Angelis, Jan Rozman: Diet-induced and mono-genetic obesity alter volatile organic compound signature in mice. 2016; J. Breath Res. 10;DOI: 10.1088/1752-7155/10/1/016009