Tiny molecules with a big impact

January 13, 2021

The human organism requires a variety of small molecules, such as sugars or fats, in order to function properly. The composition of these so-called metabolites and their interaction - the metabolism - varies from person to person and is dependent not only on external influences, such as nutrition, but also to a significant extent on natural variations in our genetic make-up. In an international study, scientists from the Berlin Institute of Health (BIH) and Charité - Universitätsmedizin Berlin joined forces with colleagues from the United Kingdom, Australia and the United States and discovered hundreds of previously unknown variations in genes that have a sometimes drastic impact on the concentration of these small molecules in the blood. The researchers have now published their findings in the journal Nature Genetics.

The concentration and composition of metabolites - small molecules in the blood or tissue fluid - provide information about biological processes in the human body. They therefore serve as important biomarkers in clinical medicine, for example in the diagnosis of diseases or in checking the effectiveness of a therapy. Interestingly, the composition of metabolites differs from person to person, independent of external influences such as illness or diet. This is because the blueprints for the proteins that influence metabolite concentration, such as enzymes and transporter proteins, also differ between individuals. Often, the tiniest genetic variants can cause a metabolic enzyme to be more or less active or a transporter protein to be more or less efficient, thus raising or lowering the concentration of metabolites.

Data analyzed from 85,000 people

The team led by Claudia Langenberg, BIH Professor of Computational Medicine, has now investigated the effect of genetic variants on 174 different metabolites. "We found a surprising number of correlations between certain genetic variants and changes in the concentration of small molecules in the blood," reports the epidemiologist. "In most cases, the genetic variants cause changes in the blueprint of key metabolism regulators, like enzymes or transporters."

To explore these correlations, Langenberg's team needed huge amounts of data. "For our studies, we used large databases that gave us the blood test results and genetic information of a total of around 85,000 people," explains Maik Pietzner, lead author of the study and a scientist in Langenberg's laboratory. "In doing so, we were able to successfully demonstrate that it is possible to jointly evaluate data from a variety of small individual studies, even across technological boundaries."

Genetic variants can contribute to common diseases

The scientists' work is highly relevant to medicine, because it can explain how naturally occurring genetic variants that influence the metabolism contribute to the onset of common diseases, such as diabetes mellitus, as well as rare diseases. For example, high levels of the amino acid serine in the blood seem to provide protection against a rare eye disease called macular telangiectasia - knowledge that opens up new therapeutic avenues. In another study, the authors were also able to show that an individual's genetic risk for altered serine metabolism can aid in the early diagnosis of this serious eye disease. They have also identified a new mechanism that explains how the disrupted transmission of signals via the GLP-2 receptor increases the risk of developing type 2 diabetes.

"What was special about our study were the extreme effects that we observed and their potential relevance for medical research," explains Langenberg. "For example, we were able to detect genetic variants that have an influence on metabolism a good three times as strong as the already known effects of more common genetic variations, for example on body mass index."

Data is only relevant if used

To enable scientists around the world to link up their particular fields of expertise with their data, the team has set up an interactive website at http://www.omicscience.org. After all, Langenberg emphasizes, data is only relevant if it can also be used: "We very much hope that these compelling examples will encourage other scientists and doctors to apply our results to their specific research or disease cases."
-end-
Luca A Lotta, Maik Pietzner, ......,Claudia Langenberg: "A cross-platform approach identifies genetic regulators of human metabolism and health." Nature Genetics 2021, DOI 10.1038/s41588-020-00751-5

About the Berlin Institute of Health (BIH)

The mission of the Berlin Institute of Health (BIH) is medical translation: transferring biomedical research findings into novel approaches to personalized prediction, prevention, diagnostics and therapy and, conversely, using clinical observations to develop new research ideas. The aim is to deliver relevant medical benefits to patients and the population at large. The BIH is also committed to establishing a comprehensive translational ecosystem as translational research area at Charité - one that places emphasis on a system-wide understanding of health and disease and that promotes change in the biomedical research culture. The BIH is funded 90 percent by the Federal Ministry of Education and Research (BMBF) and 10 percent by the State of Berlin. The two founding institutions, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), were independent member entities within the BIH until 2020. As of 2021, the BIH has been integrated into Charité as the so-called third pillar; the MDC is privileged partner of the BIH.

BIH at Charité

Related Metabolism Articles from Brightsurf:

Early trauma influences metabolism across generations
A study by the Brain Research Institute at UZH reveals that early trauma leads to changes in blood metabolites - similarly in mice and humans.

Cannabinoids decrease the metabolism of glucose in the brain
What happens when THC acts on the glial cells named astrocytes ?

New role of arginine metabolism in plant morphogenesis identified
A research team led by ExCELLS/NIBB found that arginine metabolism has a vital role in regulating gametophore shoot formation in the moss Physcomitrium patens.

Watching changes in plant metabolism -- live
Almost all life on Earth, e.g. our food and health, depend on metabolism in plants.

redHUMAN: Deciphering links between genes and metabolism
Scientists at EPFL have developed a new method that simplifies the processing of genetic-metabolic data by picking up changes in metabolism, a hallmark of numerous diseases like cancer and Alzheimer's.

Lipid metabolism controls brain development
A lipid metabolism enzyme controls brain stem cell activity and lifelong brain development.

Inhibition of sphingolipid metabolism and neurodegenerative diseases
Disrupting the production of a class of lipids known as sphingolipids in neurons improved symptoms of neurodegeneration and increased survival in a mouse model.

Viruses don't have a metabolism; but some have the building blocks for one
'Giant viruses' are many times larger than typical viruses and have more complex genomes.

New metabolism discovered in bacteria
Microbiologists at Goethe University Frankfurt have discovered how the bacterium Acetobacterium woodii uses hydrogen in a kind of cycle to conserve energy.

Protein controls fat metabolism
A protein in the cell envelope influences the rate of fatty acid uptake in cells.

Read More: Metabolism News and Metabolism Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.