Metabolomics: Hemogram in Megapixels

15. September 2010
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Why does sport keep us healthy? Why don’t I tolerate food tasting so good for others? And why does this drug against cancer not work for me? Where geneticists don’t have the answers, metabolomics come into the game – the analysis of metabolism.

It cannot be just the food. Often it’s the jealous looks of siblings trying diet after diet and still having more problems with their weight than the daughter gobbling huge loads down without gaining weight. “Despite a nearly identical genome – 99.9 percent – we are all looking very different and these differences seem to reflect also in the metabolism.” Hannelore Daniel at the Technical University Munich/Germany has devoted herself to a young special field: Metabolomics.

Comprehensive analysis of the metabolism

Just like with the other “-omics“ disciplines, metabolomicists target to capture all processes in the body. In addition to genetic material and the proteins, it’s the metabolites representative for differences and commonalities in the individual’s metabolism. Metabolites are components of macromolecules, carriers of energy, intermediate products of the different biochemical processes. Among them are also hormones or regulatory factors in the body.

Which tools do the scientists use? One of the most important instruments in metabolomics is the mass spectrometer. Mostly after an initial chromatographic separation of the sample, thus known and so far unidentified molecules can be registered qualitatively and quantitatively. Accordingly, the expert differentiates between “targeted” and “non-targeted metabolomics”. New methods allow the researchers to analyse a thousand samples per week and also determination of quantities of hundreds of lipids, sugar molecules or amino-acids. With low flow-rates but higher solution, the detectors are able to expand the catalogue of relevant factors in metabolism more and more.

Athletes: Efficient fat burners

An article of a research group at Harvard University and two large hospitals in Boston/USA was published recently in the biomedical professional magazine “Science Translational Medicine”. Their studies might provide an important answer to the question: What’s so healthy about sports for body and soul? Instead of a big blood work, Robert Gerszten and his colleagues determined more than 200 metabolites of about 90 athletes and non-athletes before and after a ten-minute run or ergometer training. In 21 of the factors, the values changed significantly. But not just that: The recorded pictures of the metabolism also allowed to distinguish fit and not so fit test persons.

For example the level of glycerine was doubled in the blood of athletes. Less trained people had an increase of only 60-70 percent. One group of the runners, which participated in the Boston Marathon before, even reached 1128 percent of this degradation product for fat burning. Also their level of amino-acids in blood circulation is very low. Thus the researchers assume that the endurance athletes degrade those protein components while running in order to keep the glucose level stable.

Therapy approach for metabolic syndrome?

Metabolites not associated with sports by physiologists so far, appeared in the analysis. Like niacinamide. This vitamin derivate promotes insulin output and influences sugar regulation. A combination of five of the measured metabolites, the researchers added to a muscle cell culture. Thus they achieved an increase of the regulation factor “nur77”. This gene plays an important role in degradation of sugar and fat. The metabolites used only work in combination but not individually. This effect can be proven in animal tests as well. 30 minutes of mice running the wheel increased expression of this factor by five times. Metabolomics experts speculate that perhaps such a metabolite combination might be a future perspective for treatment of people with metabolic syndrome not capable of athletic endurance training. Robert Gerszten says that another application could be for example the development of special athletes’ beverages providing replacement of degraded metabolites.

nstitutes in Germany are also working hard to raise the infant “metabolomics”. A few weeks ago Munich organized the first international congress in Germany with the topic “Metabolomics & More – The Impact of Metabolomics on the Life Sciences” with about 400 participants. The Hemholtz Center in Munich and the technical university have combined forces to make an own large study (HuMet) on the topic: 15 young men with similar BMI received a standardized fluid diet after a longer fasting period. After a short termed increase of blood sugar levels, the devices displayed significant differences in decline of the level to normal stage. Now the researchers of the “Munich Functional Metabolomics Initiative” want to study the background of these individual differences. With a little luck, this might lead to an improved individualized therapy for metabolic disorders.

In Berlin, Carsten Denkert searches for new biomarkers in breast cancer with EU funding, in Regensburg/Germany Gerd Schmitz is looking for changes in fat metabolism in vascular- and metabolic disorders. “But we have to further develop these methods in order to do justice to the complexity of our metabolism. Today we are only in the stage of development of the digital camera in the eighties”, says Thomas Hofmann at the Munich TU and co-worker in the metablomics initiative. “We have to increase the solution of our analytic camera to get the best possible and sharp picture of all metabolic products.”

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Dr. Roeland Van Hoof
Dr. Roeland Van Hoof

I am advising Patients with diabetes, hypertension, COPD and astma to chance their lifestyle, eating habits and do duration and endurance exercises on regular basis.
How would this knowledge of metabolomics influence our daily treatment? ie. Could this treatment be adapted specifically for each patient according to his metabolomic profile? Could we give athletes more specific exercise/sports advices, to improve/optimize their metabolomic profile and trough that optimize sportive output (endurance, speed, muscle function)?
How can we do such in daily practice?

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