Basic research requires a great deal of perseverance before it bears fruit, if it ever does. This is a simple fact. So it is all the more gratifying when the fruits of researchers’ labour ripen - and when even more are on the way. Professor Antje Körner found her calling early on in her medical training: obesity and metabolism in children. "We knew in the early 2000s at the paediatric clinic led by Professor Wieland Kiess that metabolism and disease were linked to the development of obesity. It was then that I embarked on the first studies in this area, sifting through mountains of patient records for clinical data, in search of patterns and anomalies. That was my starting point for the Leipzig obesity cohorts and further clinical trials. Today, we can say we have come a long way."
The cohorts of children and adolescents with and without obesity have been established and continuously developed over the years. Subjects are part of the large-scale LIFE Child study and recruited through the University’s paediatric obesity clinic and the Faculty of Medicine’s Integrated Research and Treatment Center (IFB) AdiposityDiseases. The cohorts are now yielding comparative data, where a child’s upbringing is recorded very broadly in order to identify environmental risk factors. "In LIFE Child, we have a unique resource that is second to none."
A highly complex puzzle Antje Körner’s approach has broadened considerably over the years. A professor of paediatric research, she combines experimental, clinical, genetic and epidemiological studies. Her ultimate goal is to gain a better understanding of the interplay between risk factors, predisposition and clinical progression to enable more targeted and effective interventions for children and adolescents with obesity and diabetes. She sums it up as follows: "My philosophy is that a complex disease requires a complex approach."
And the fruits of her research? Most recently, Antje Körner received the Elliot Joslin Prize from the German Diabetes Society and the Research Award from the European Society for Paediatric Endocrinology. She was also behind the remarkable discovery of a new gene mutation which affects hunger control. A missing piece of the puzzle in monogenic obesity research. She is pleased with her discovery: "It’s not often as a researcher that you discover something completely new. It was all possible thanks to the strong interdisciplinary cooperation on the Leipzig campus for our main topic and also the openness to other approaches. And of course my creative team."
The multiplier effect Human genetics and energy metabolism are designed to conserve and store energy in the form of fat. They are not adapted to today’s lifestyle of excess nutrients and lack of exercise. And the consequences are serious: obesity and related diseases, health costs running into billions. The World Health Organisation defines obesity as the accumulation of excess fat in the body that poses a risk to health. A fifth of children in Germany are already overweight, putting them at increased risk of diabetes, fatty liver disease, stroke, heart attack, cancer and premature death. Some people are particularly susceptible or genetically predisposed, some risks develop during pregnancy and most are exacerbated by environmental factors. Many factors are at work simultaneously. With this in mind, there is no denying just how complex, far-reaching and socially relevant the issue of modern diseases, and obesity in particular, is.
Children and adolescents still fall through the cracks far too often because research, diagnosis and treatment are all focused on adults.
A unique place to do research Researching the mechanisms and treatment of obesity has been a focus of university research in Leipzig for many years. Leipzig benefits from a multidisciplinary research ecosystem with diverse groups and orientations - including genetics, environmental influences, metabolism, the role of abdominal fat, gender, food culture, mental health, therapeutic interventions, and much more. Aspects relating to children and young people are taken into account across the board, which is exceptional and a unique selling point for Leipzig. Unfortunately, as Antje Körner points out, lifestyle diseases are still generally underrepresented in paediatrics: "Children and adolescents still fall through the cracks far too often because research, diagnosis and treatment are all focused on adults. At conferences, my work is often seen as niche or as pushing boundaries." Traditionally, paediatric diabetology has focused on type 1 diabetes. In contrast, type 2 diabetes and obesity have long been considered diseases of affluence or age. It is only in recent years that more attention has been paid to children, as knowledge of early causes has filtered through, partly as a result of the work being done in Leipzig.
Lack of attention for affected children At this point in the conversation, Antje Körner’s face becomes very serious. "The advice to children with severe obesity to exercise more and eat less is widespread, but falls far short of what is needed. By the time they come to our obesity walk-in centre, too much has already happened. Children have little chance of changing anything because they have little influence over epidemiologically proven risk factors such as their parents’ weight or social status, their living environment or their eating habits. But they usually live with the consequences for the rest of their lives. Obesity is a chronic disease." She adds that the lack of attention from researchers and the pharmaceutical industry, as well as from policy-makers and society at large, is a serious mistake. "Our research supports the hypothesis that excessive weight gain in children under the age of six can be an early sign of later disease. The frequency is alarmingly high. The majority of children and young people who are overweight will still be overweight as adults. Between 30 and 50 per cent of children between the ages of five and six show the first signs of a metabolic disorder. This also applies to what is sometimes called adult-onset diabetes, because the centres of energy intake are already dysregulated. We were able to demonstrate these effects in a large longitudinal study with more than 51,000 children from birth to adolescence." This makes it quite clear why a lifestyle change alone can no longer lead to lasting success. A more nuanced approach to treatment is needed, taking into account living conditions and analysing individual risk factors. "We are seeing an alarming trend worldwide. The risk of dying as a relatively young adult is quite high. We all need to be aware of the seriousness of the problem. You can see how difficult it is already to implement a Nutri-Score or a ban on advertising sugary foods in children’s programmes in Germany. We also need to have the confidence to make effective treatment options available to children."
What role can research play First, many more studies are needed, then better and more targeted diagnostic tools, and finally appropriate drugs. This is because values from adults, such as thresholds for laboratory parameters or blood glucose, cannot simply be transferred. "This is another area where the global community is not well positioned," says Antje Körner. "Leipzig, on the other hand, has good clinical research. We have recently shown that these values are dynamic over the years and that we actually need age-specific thresholds. We are interested in gaining a comprehensive understanding of such relationships and the mechanisms behind them, both biologically and in laboratory experiments, and genetically and molecularly. We are now in an excellent position, built up over the years and through various research alliances. Obesity research in itself is also anchored here with outstanding scientists such as Professor Michael Stumvoll, Professor Wieland Kiess and Professor Matthias Blüher. One of our main areas of expertise is now adipose tissue. Obesity research in Leipzig has gained a national and even international reputation. The current highlight of the journey for me is the proposed cluster."
Obesity research in Leipzig has gained a national and even international reputation.
Strength in numbers The list of projects and scientific collaborations on the journey that Antje Körner alludes to is long, and the cross-connections between disciplines and research institutions seem to interlock in a bold yet coherent way. And everywhere, the LIFE Child cohorts are proving to be a treasure trove of data.
Antje Körner is a member of the board of Collaborative Research Centre 1052, Obesity Mechanisms. Its Adipokines research group includes her aforementioned project on monogenic forms of obesity together with biologist and early career researcher Dr Kathrin Landgraf. Another deals with cardiometabolic dysfunction. In July 2023, she took up the professorship for metabolism research at the Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) in Leipzig, a joint institution with Helmholtz Munich. It investigates the molecular basis to enable precise therapies through a clinical translational research approach. Antje Körner is delighted that the professorship offers the opportunity to take translational research for children to a higher level. The next largest research alliance is a planned project in clinical metabolic research, for which Leipzig’s life science researchers are applying for funding under the German Excellence Strategy. The aim is to research modern diseases and their long-term consequences over the entire lifespan and by analysing individual metabolic processes. Of course, children and young people are also an important part of this.
Success develops its own momentum
And finally, a look at the near future: the existing regional research network SaxoChiLD Leipzig-Dresden (Saxonian Child Health Innovation Leipzig-Dresden) will become one of seven nationwide sites of the new German Centre for Child and Adolescent Health (DZKJ) and will start work in Leipzig in early 2024. With a research focus on the early origins of health and disease, it is the first German health research centre in which Leipzig is a full partner. Antje Körner is hopeful: "Our growing strength has created its own momentum. As successes become more visible, this attracts further funding and resources. This will enable us to build on the path we have taken and also attract the best minds. With this overall package, we can lead research in children and adolescents in Germany. No other research site is capable of doing this in this way. Cohorts and biobanks combined with clinical observation, mechanistic research and genetics: this is something quite unique - and all in an environment of unconventional openness."
Customised precision medicine as a necessary goal A healthy diet and sufficient exercise are still essential for prevention. But what about treatment if the disease has already developed? "Finding the right treatment for obese patients is extremely complex because the problems are multifaceted. It is important to be highly attentive to the child and their family; they may require psychological support, nutritional guidance and exercise therapy. These additional costs are necessary but not covered in Germany. From a clinical and economic point of view, we constantly have to justify this," says Antje Körner. According to the vision, once the mechanisms of development are better understood, it will be easier to assess individual risk more effectively and to counteract it with newly developed treatment approaches, including drugs tailored to the child’s body.
There are a large number of approved diabetes drugs for adults, but currently only three for children: insulin, which was developed over a century ago; metformin, which was approved for children at the turn of the millennium and can only be used in cases of overt diabetes; and more recently, incretin agonists, new molecules that intervene in biological responses. "This is a stark illustration of the decades-long lag in science and treatment for children."
Highly effective drugs are offering hope for adults with obesity. They are based on incretins, hormones originating in the intestine that control food intake and energy metabolism - a milestone development from Helmholtz Munich. In some cases, body weight can be reduced by more than 20 per cent, which approaches the results of gastric banding. "This has never been seen before. For the first time, we have a drug that we can work with successfully." Paediatrician Antje Körner hopes that such advances in pharmacology will benefit children sooner. "By joining forces with Helmholtz Munich, we have a good chance of eventually being able to offer this therapy. In young people in particular, we probably have a window of opportunity for radical change with lasting success, because we can intervene relatively early in the pathological process. Some studies have already shown this. We must take advantage of this window of opportunity!" Now, the researcher adds, is an exciting time because a lot is happening. She enjoys pushing conceptual boundaries, even in the face of opposition if necessary. The way Antje Körner says this leaves no room for doubt.
Diana Smikalla
Professor Antje Körner... researches the causes and consequences of metabolic diseases in children. Born in 1973, she grew up in Plauen, Saxony and studied medicine in Leipzig. During research stays in the US and Düsseldorf, she began to focus on her topic early on. She has been a medical researcher at Leipzig since 2001. She is currently Professor of Metabolism at HI-MAG, head of the Center for Pediatric Research (CPL), and senior physician for paediatrics and adolescent medicine at the University of Leipzig Medical Center.
About the joint project on clinical metabolic research
Our metabolism is based on ancient, fundamentally human, but also recently acquired mechanisms that are increasingly causing disease in our modern society: they facilitate a pathological increase in blood lipids and blood sugar, known as diabetes mellitus, or the development of fatty liver disease. This in turn leads to an increased risk of serious cardiovascular diseases, such as heart attacks and strokes, as well as some forms of cancer.
Some people are more susceptible than others. The same is true of therapies - some people respond and others do not. Lifelong risks can develop in early childhood, while still in the womb, or through hereditary exposure. The researchers want to establish a clinical research centre dedicated to understanding and improving the burden of disease caused by metabolic disorders. The aim is to develop high-response therapeutic approaches based on individual metabolic disorders rather than indiscriminately targeting risk factors.
